The global aging population has led to an increasing burden of age-related orthopedic diseases, seriously imposing social and economic pressures. Although exercise has been proven to have a protective effect on the musculoskeletal system, diseases themselves often restrict patients from engaging in physical activity. Exercise mimetics, as a pharmacological intervention that can simulate or enhance the benefits of exercise, offer new treatment options for such patients.
Recent Advances:
Exercise mimetics modulate oxidative stress, inflammatory responses, and apoptosis to enhance bone mineral density, improve trabecular microarchitecture, facilitate cartilage nourishment, and augment muscular strength and endurance. They have shown promising therapeutic potential in disease models such as osteoarthritis, intervertebral disc degeneration, osteoporosis, and sarcopenia. Some compounds such as metformin and resveratrol have been used in clinical research.
Critical Issues:
This review summarizes the mechanism of action and the latest research progress on exercise mimetics in degenerative orthopedic diseases and analyzes the current translational challenges and limitations in the research.
Future Directions:
Future research should further clarify the tissue-specific effects of exercise mimetics, the long-term safety of their use, and individual differences in their therapeutic efficacy. Meanwhile, developing targeted delivery systems, optimizing bioavailability, and promoting more rigorously designed clinical studies will help achieve wide application of exercise mimetics in the treatment of orthopedic diseases. Antioxid. Redox Signal. 44, 488–527.
AbedÉ, DelalandreA, LajeunesseD. Beneficial effect of resveratrol on phenotypic features and activity of osteoarthritic osteoblasts. Arthritis Res Ther, 2017; 19(1):151; doi: 10.1186/s13075-017-1365-2
Abou-SamraM, DubuissonN, MarinoA, et al.Striking cardioprotective effects of an adiponectin receptor agonist in an aged mouse model of Duchenne muscular dystrophy. Antioxidants (Basel), 2024; 13(12):1551; doi: 10.3390/antiox13121551
4.
Abou-SamraM, SelvaisCM, BoursereauR, et al.AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy. J Cachexia Sarcopenia Muscle, 2020; 11(2):518–533; doi: 10.1002/jcsm.12531
5.
AhujaP, NgCF, PangBPS, et al.Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice. Autophagy, 2022; 18(6):1367–1384; doi: 10.1080/15548627.2021.1985257
6.
AlexA, LuoQ, MathewD, et al.Metformin corrects abnormal circadian rhythm and kir4.1 channels in diabetes. Invest Ophthalmol Vis Sci, 2020; 61(6):46; doi: 10.1167/iovs.61.6.46
7.
AlimoradiN, TahamiM, FirouzabadiN, et al.Metformin attenuates symptoms of osteoarthritis: Role of genetic diversity of Bcl2 and CXCL16 in OA. Arthritis Res Ther, 2023; 25(1):35; doi: 10.1186/s13075-023-03025-7
8.
AlwaySE, McCroryJL, KearcherK, et al.Resveratrol enhances exercise-induced cellular and functional adaptations of skeletal muscle in older men and women. J Gerontol A Biol Sci Med Sci, 2017; 72(12):1595–1606; doi: 10.1093/gerona/glx089
9.
AmoasiiL, Sanchez-OrtizE, FujikawaT, et al.NURR1 activation in skeletal muscle controls systemic energy homeostasis. Proceedings of the National Academy of Sciences of the United States of America, 2019; 116(23):11299–11308; doi: 10.1073/pnas.1902490116
10.
AndreuxPA, Blanco-BoseW, RyuD, et al.The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab, 2019; 1(6):595–603; doi: 10.1038/s42255-019-0073-4
11.
AnguloJ, El AssarM, Álvarez-BustosA, et al.Physical activity and exercise: Strategies to manage frailty. Redox Biol, 2020; 35:101513; doi: 10.1016/j.redox.2020.101513
12.
AoX, LiK, ChenY, et al.Inhibition of TrkB-BDNF positive feedback loop attenuates intervertebral disc degeneration and low back pain in a composite mouse model. Brain Behav Immun, 2025; 128:37–53; doi: 10.1016/j.bbi.2025.03.029
13.
BangS, KimDE, KangHT, et al.Metformin restores autophagic flux and mitochondrial function in late passage myoblast to impede age-related muscle loss. Biomed Pharmacother, 2024; 180:116981; doi: 10.1016/j.biopha.2024.116981
14.
BaoZ, LiZ, ZhaoM, et al.The effects of acute carbohydrate supplementation on inflammatory cytokines in individuals performing different exercise intensities: A systematic review and meta-analysis. Crit Rev Food Sci Nutr, 2025:1–13; doi: 10.1080/10408398.2025.2548009
15.
Bar-ShaiM, CarmeliE, LjubuncicP, et al.Exercise and immobilization in aging animals: The involvement of oxidative stress and NF-kappaB activation. Free Radic Biol Med, 2008; 44(2):202–214; doi: 10.1016/j.freeradbiomed.2007.03.019
16.
BassezG, AudureauE, HogrelJY, et al.Improved mobility with metformin in patients with myotonic dystrophy type 1: A randomized controlled trial. Brain, 2018; 141(10):2855–2865; doi: 10.1093/brain/awy231
17.
BeheraJ, IsonJ, VoorMJ, et al.Exercise-linked skeletal irisin ameliorates diabetes-associated osteoporosis by inhibiting the oxidative damage-dependent miR-150-FNDC5/Pyroptosis Axis. Diabetes, 2022; 71(12):2777–2792; doi: 10.2337/db21-0573
18.
BelavýDL, AlbrachtK, BruggemannGP, et al.Can exercise positively influence the intervertebral disc? Sports Med, 2016; 46(4):473–485; doi: 10.1007/s40279-015-0444-2
19.
BillonC, SitaulaS, BanerjeeS, et al.Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol, 2023; 18(4):756–771; doi: 10.1021/acschembio.2c00720
20.
BishopDJ, LeeMJ, PicardM. Exercise as mitochondrial medicine: How does the exercise prescription affect mitochondrial adaptations to training? Annu Rev Physiol, 2025; 87(1):107–129; doi: 10.1146/annurev-physiol-022724-104836
21.
BlazevR, CarlCS, NgYK, et al.Phosphoproteomics of three exercise modalities identifies canonical signaling and C18ORF25 as an AMPK substrate regulating skeletal muscle function. Cell Metab, 2022; 34(10):1561–1577.e1569; doi: 10.1016/j.cmet.2022.07.003
BoonH, BosselaarM, PraetSF, et al.Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients. Diabetologia, 2008; 51(10):1893–1900; doi: 10.1007/s00125-008-1108-7
24.
BörgesonE, WalleniusV, SyedGH, et al.AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin. Diabetologia, 2017; 60(4):729–739; doi: 10.1007/s00125-017-4211-9
25.
BoströmP, WuJ, JedrychowskiMP, et al.A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 2012; 481(7382):463–468; doi: 10.1038/nature10777
26.
BouléNG, RobertC, BellGJ, et al.Metformin and exercise in type 2 diabetes: Examining treatment modality interactions. Diabetes Care, 2011; 34(7):1469–1474; doi: 10.2337/dc10-2207
27.
BriccaA, HarrisLK, JägerM, et al.Benefits and harms of exercise therapy in people with multimorbidity: A systematic review and meta-analysis of randomised controlled trials. Ageing Res Rev, 2020; 63:101166; doi: 10.1016/j.arr.2020.101166
28.
BrockhoffM, RionN, ChojnowskaK, et al.Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I. J Clin Invest, 2017; 127(2):549–563; doi: 10.1172/jci89616
29.
CaiL, SwethaM, RajiA, et al.Mitochondria-targeted therapy with metformin and MitoQ reduces oxidative stress, improves mitochondrial function, and restores metabolic homeostasis in a murine model of Gulf War Illness. Redox Biol, 2025; 85:103714; doi: 10.1016/j.redox.2025.103714
30.
CameraDM, SmilesWJ, HawleyJA. Exercise-induced skeletal muscle signaling pathways and human athletic performance. Free Radic Biol Med, 2016; 98:131–143; doi: 10.1016/j.freeradbiomed.2016.02.007
31.
CamporezJP, PetersenMC, AbudukadierA, et al.Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice. Proceedings of the National Academy of Sciences of the United States of America, 2016; 113(8):2212–2217; doi: 10.1073/pnas.1525795113
32.
CarapetoP, IwasakiK, HelaF, et al.Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence. Nat Metab, 2024; 6(10):1976–1990; doi: 10.1038/s42255-024-01130-8
33.
ChanWS, NgCF, PangBPS, et al.Exercise-induced BDNF promotes PPARδ-dependent reprogramming of lipid metabolism in skeletal muscle during exercise recovery. Sci Signal, 2024; 17(828):eadh2783; doi: 10.1126/scisignal.adh2783
34.
ChenD, XiaD, PanZ, et al.Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo. Cell Death Dis, 2016; 7(10):e2441; doi: 10.1038/cddis.2016.334
35.
ChenH, ChenF, HuF, et al.MicroRNA-224-5p nanoparticles balance homeostasis via inhibiting cartilage degeneration and synovial inflammation for synergistic alleviation of osteoarthritis. Acta Biomater, 2023a;167:401–415; doi: 10.1016/j.actbio.2023.06.010
36.
ChenJ, XieJJ, JinMY, et al.Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration. Cell Death Dis, 2018a;9(2):56; doi: 10.1038/s41419-017-0085-5
37.
ChenT, PengY, HuW, et al.Irisin enhances chondrogenic differentiation of human mesenchymal stem cells via Rap1/PI3K/AKT axis. Stem Cell Res Ther, 2022; 13(1):392; doi: 10.1186/s13287-022-03092-8
38.
ChenX, LiX, ZhangW, et al.Activation of AMPK inhibits inflammatory response during hypoxia and reoxygenation through modulating JNK-mediated NF-κB pathway. Metabolism, 2018b;83:256–270; doi: 10.1016/j.metabol.2018.03.004
39.
ChenX, ZhangY, DengZ, et al.Keratocan improves muscle wasting in sarcopenia by promoting skeletal muscle development and fast-twitch fibre synthesis. J Cachexia Sarcopenia Muscle, 2025; 16(1):e13724; doi: 10.1002/jcsm.13724
40.
ChenX, ZhuX, WeiA, et al.Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis. Bone Res, 2021a;9(1):15; doi: 10.1038/s41413-020-00128-8
41.
ChenY, LiuY, JiangK, et al.Linear ubiquitination of LKB1 activates AMPK pathway to inhibit NLRP3 inflammasome response and reduce chondrocyte pyroptosis in osteoarthritis. J Orthop Translat, 2023b;39:1–11; doi: 10.1016/j.jot.2022.11.002
42.
ChenY, ZhangT, WanL, et al.Early treadmill running delays rotator cuff healing via Neuropeptide Y mediated inactivation of the Wnt/β-catenin signaling. J Orthop Translat, 2021b;30:103–111; doi: 10.1016/j.jot.2021.08.004
43.
ChoiHY, KimS, ParkJW, et al.Implication of circulating irisin levels with brown adipose tissue and sarcopenia in humans. J Clin Endocrinol Metab, 2014; 99(8):2778–2785; doi: 10.1210/jc.2014-1195
44.
CohenS, NathanJA, GoldbergAL. Muscle wasting in disease: Molecular mechanisms and promising therapies. Nat Rev Drug Discov, 2015; 14(1):58–74; doi: 10.1038/nrd4467
45.
ColaianniG, CuscitoC, MongelliT, et al.The myokine irisin increases cortical bone mass. Proceedings of the National Academy of Sciences of the United States of America, 2015; 112(39):12157–12162; doi: 10.1073/pnas.1516622112
46.
CollinsJA, KapustinaM, BolducJA, et al.Sirtuin 6 (SIRT6) regulates redox homeostasis and signaling events in human articular chondrocytes. Free Radic Biol Med, 2021; 166:90–103; doi: 10.1016/j.freeradbiomed.2021.01.054
47.
CollinsJA, KimCJ, ColemanA, et al.Cartilage-specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis severity in mice. Ann Rheum Dis, 2023; 82(11):1464–1473; doi: 10.1136/ard-2023-224385
48.
CollinsJA, MootsRJ, CleggPD, et al.Resveratrol and N-acetylcysteine influence redox balance in equine articular chondrocytes under acidic and very low oxygen conditions. Free Radic Biol Med, 2015; 86:57–64; doi: 10.1016/j.freeradbiomed.2015.05.008
DankbarB, FennenM, BrunertD, et al.Myostatin is a direct regulator of osteoclast differentiation and its inhibition reduces inflammatory joint destruction in mice. Nat Med, 2015; 21(9):1085–1090; doi: 10.1038/nm.3917
55.
de Lima JuniorEA, YamashitaAS, PimentelGD, et al.Doxorubicin caused severe hyperglycaemia and insulin resistance, mediated by inhibition in AMPk signalling in skeletal muscle. J Cachexia Sarcopenia Muscle, 2016; 7(5):615–625; doi: 10.1002/jcsm.12104
56.
de MarañónAM, Díaz-PozoP, CanetF, et al.Metformin modulates mitochondrial function and mitophagy in peripheral blood mononuclear cells from type 2 diabetic patients. Redox Biol, 2022; 53:102342; doi: 10.1016/j.redox.2022.102342
57.
de SousaCV, SalesMM, RosaTS, et al.The antioxidant effect of exercise: A systematic review and meta-analysis. Sports Med, 2017; 47(2):277–293; doi: 10.1007/s40279-016-0566-1
58.
DelezieJ, WeihrauchM, MaierG, et al.BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle. Proceedings of the National Academy of Sciences of the United States of America, 2019; 116(32):16111–16120; doi: 10.1073/pnas.1900544116
59.
DennisonEM, SayerAA, CooperC. Epidemiology of sarcopenia and insight into possible therapeutic targets. Nat Rev Rheumatol, 2017; 13(6):340–347; doi: 10.1038/nrrheum.2017.60
60.
D’HulstG, Soro-ArnaizI, MasscheleinE, et al.PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase. Nat Commun, 2020; 11(1):174; doi: 10.1038/s41467-019-13889-6
61.
DimitriadisAT, PapagelopoulosPJ, SmithFW, et al.Intervertebral disc changes after 1 h of running: A study on athletes. J Int Med Res, 2011; 39(2):569–579; doi: 10.1177/147323001103900226
62.
DingP, YangR, LiC, et al.Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway. Crit Care, 2023; 27(1):196; doi: 10.1186/s13054-023-04488-5
63.
DingX, JianT, WuY, et al.Ellagic acid ameliorates oxidative stress and insulin resistance in high glucose-treated HepG2 cells via miR-223/keap1-Nrf2 pathway. Biomed Pharmacother, 2019; 110:85–94; doi: 10.1016/j.biopha.2018.11.018
DongJQ, RossulekM, SomayajiVR, et al.Pharmacokinetics and pharmacodynamics of PF-05231023, a novel long-acting FGF21 mimetic, in a first-in-human study. Br J Clin Pharmacol, 2015; 80(5):1051–1063; doi: 10.1111/bcp.12676
66.
DongW, ZhangK, WangX, et al.SIRT1 alleviates Cd nephrotoxicity through NF-κB/p65 deacetylation-mediated pyroptosis in rat renal tubular epithelial cells. Sci Total Environ, 2024; 929:172392; doi: 10.1016/j.scitotenv.2024.172392
67.
DuQ, XueJ, FanD, et al.CircZNF418 alleviates oxidative stress-induced cartilage endplate degeneration by stabilizing Sox9 through HuR. J Mol Histol, 2025; 56(4):242; doi: 10.1007/s10735-025-10528-x
68.
DuanZX, TuC, LiuQ, et al.Adiponectin receptor agonist AdipoRon attenuates calcification of osteoarthritis chondrocytes by promoting autophagy. J Cell Biochem, 2020; 121(5–6):3333–3344; doi: 10.1002/jcb.29605
69.
EgashiraK, KajiyaH, TsutsumiT, et al.AMPK activation enhances osteoblast differentiation on a titanium disc via autophagy. Int J Implant Dent, 2024; 10(1):2; doi: 10.1186/s40729-024-00525-2
70.
EnsrudKE, CrandallCJ. Osteoporosis. Ann Intern Med, 2024; 177(1):Itc1–Iitc16; doi: 10.7326/aitc202401160
71.
FanW, EvansRM. Exercise mimetics: Impact on health and performance. Cell Metab, 2017; 25(2):242–247; doi: 10.1016/j.cmet.2016.10.022
72.
FanW, WaizeneggerW, LinCS, et al.PPARδ promotes running endurance by preserving glucose. Cell Metab, 2017; 25(5):1186–1193.e1184; doi: 10.1016/j.cmet.2017.04.006
73.
FengZ, BaiL, YanJ, et al.Mitochondrial dynamic remodeling in strenuous exercise-induced muscle and mitochondrial dysfunction: Regulatory effects of hydroxytyrosol. Free Radic Biol Med, 2011; 50(10):1437–1446; doi: 10.1016/j.freeradbiomed.2011.03.001
74.
FernandesIG, OliveiraLM, AndradeMMS, et al.Resveratrol upregulates antioxidant factors expression and downmodulates interferon-inducible antiviral factors in aging. Int J Mol Sci, 2025; 26(5):2345; doi: 10.3390/ijms26052345
75.
FinaudJ, LacG, FilaireE. Oxidative stress: Relationship with exercise and training. Sports Med, 2006; 36(4):327–358; doi: 10.2165/00007256-200636040-00004
76.
ForcinaL, MianoC, MusaròA. The physiopathologic interplay between stem cells and tissue niche in muscle regeneration and the role of IL-6 on muscle homeostasis and diseases. Cytokine Growth Factor Rev, 2018; 41:1–9; doi: 10.1016/j.cytogfr.2018.05.001
77.
FritzenAM, MadsenAB, KleinertM, et al.Regulation of autophagy in human skeletal muscle: Effects of exercise, exercise training and insulin stimulation. J Physiol, 2016; 594(3):745–761; doi: 10.1113/jp271405
78.
FuLY, YangY, TianH, et al.Central administration of AICAR attenuates hypertension via AMPK/Nrf2 pathway in the hypothalamic paraventricular nucleus of hypertensive rats. Eur J Pharmacol, 2024; 974:176373; doi: 10.1016/j.ejphar.2024.176373
79.
FuX, GongLF, WuYF, et al.Urolithin A targets the PI3K/Akt/NF-κB pathways and prevents IL-1β-induced inflammatory response in human osteoarthritis: In vitro and in vivo studies. Food Funct, 2019; 10(9):6135–6146; doi: 10.1039/c9fo01332f
80.
FuY, HouJ, YangQ, et al.Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis. J Nanobiotechnology, 2025; 23(1):486; doi: 10.1186/s12951-025-03543-3
81.
Gali RamamoorthyT, LavernyG, SchlagowskiAI, et al.The transcriptional coregulator PGC-1β controls mitochondrial function and anti-oxidant defence in skeletal muscles. Nat Commun, 2015; 6:10210; doi: 10.1038/ncomms10210
82.
Gallego-SellesA, Galvan-AlvarezV, Martinez-CantonM, et al.Fast regulation of the NF-κB signalling pathway in human skeletal muscle revealed by high-intensity exercise and ischaemia at exhaustion: Role of oxygenation and metabolite accumulation. Redox Biol, 2022; 55:102398; doi: 10.1016/j.redox.2022.102398
83.
Gallego-SellesA, Martin-RinconM, Martinez-CantonM, et al.Regulation of Nrf2/Keap1 signalling in human skeletal muscle during exercise to exhaustion in normoxia, severe acute hypoxia and post-exercise ischaemia: Influence of metabolite accumulation and oxygenation. Redox Biol, 2020; 36:101627; doi: 10.1016/j.redox.2020.101627
84.
GallotYS, DurieuxAC, CastellsJ, et al.Myostatin gene inactivation prevents skeletal muscle wasting in cancer. Cancer Res, 2014; 74(24):7344–7356; doi: 10.1158/0008-5472.Can-14-0057
85.
GanZ, FuT, KellyDP, et al.Skeletal muscle mitochondrial remodeling in exercise and diseases. Cell Res, 2018; 28(10):969–980; doi: 10.1038/s41422-018-0078-7
86.
GaoY, YuS, ChenM, et al.cFLIP(S) regulates alternative NLRP3 inflammasome activation in human monocytes. Cell Mol Immunol, 2023; 20(10):1203–1215; doi: 10.1038/s41423-023-01077-y
87.
GengZ, SunT, YuJ, et al.Cinobufagin suppresses lipid peroxidation and inflammation in osteoporotic mice by promoting the delivery of miR-3102-5p by macrophage-derived exosomes. Int J Nanomedicine, 2024; 19:10497–10512; doi: 10.2147/ijn.S483849
88.
GowlerPRW, LiL, WoodhamsSG, et al.Peripheral brain-derived neurotrophic factor contributes to chronic osteoarthritis joint pain. Pain, 2020; 161(1):61–73; doi: 10.1097/j.pain.0000000000001694
89.
GrabowskaK, GrabowskiM, MorysJ, et al.Age-dependent neuroinflammation response to voluntary wheel running and Metformin treatment in the frontal cortex of ovariectomized female mice. Sci Rep, 2025; 15(1):26382; doi: 10.1038/s41598-025-10014-0
90.
Grujić-MilanovićJ, JaćevićV, MiloradovićZ, et al.Resveratrol improved kidney function and structure in malignantly hypertensive rats by restoration of antioxidant capacity and nitric oxide bioavailability. Biomed Pharmacother, 2022; 154:113642; doi: 10.1016/j.biopha.2022.113642
91.
GuH, LiK, LiX, et al.Oral resveratrol prevents osteoarthritis progression in C57BL/6J mice fed a high-fat diet. Nutrients, 2016; 8(4):233; doi: 10.3390/nu8040233
92.
GuoM, YaoJ, LiJ, et al.Irisin ameliorates age-associated sarcopenia and metabolic dysfunction. J Cachexia Sarcopenia Muscle, 2023; 14(1):391–405; doi: 10.1002/jcsm.13141
93.
HaidetAM, RizoL, HandyC, et al.Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Proceedings of the National Academy of Sciences of the United States of America, 2008; 105(11):4318–4322; doi: 10.1073/pnas.0709144105
94.
HallDT, GrissT, MaJF, et al.The AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation-associated cachectic muscle wasting. EMBO Mol Med, 2018; 10(7):e8307; doi: 10.15252/emmm.201708307
95.
HanYQ, MingSL, WuHT, et al.Myostatin knockout induces apoptosis in human cervical cancer cells via elevated reactive oxygen species generation. Redox Biol, 2018; 19:412–428; doi: 10.1016/j.redox.2018.09.009
96.
HaramizuS, AsanoS, ButlerDC, et al.Dietary resveratrol confers apoptotic resistance to oxidative stress in myoblasts. J Nutr Biochem, 2017; 50:103–115; doi: 10.1016/j.jnutbio.2017.08.008
97.
HardieDG, RossFA, HawleySA. AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol, 2012; 13(4):251–262; doi: 10.1038/nrm3311
98.
HeH, HuangC, HuangH, et al.Zn(2+)-driven metformin conjugated with siRNA attenuates osteoarthritis progression by inhibiting NF-κB signaling and activating autophagy. Biomaterials, 2025; 319:123210; doi: 10.1016/j.biomaterials.2025.123210
99.
HeX, WuZ, JiangJ, et al.Urolithin a protects against hypoxia-induced pulmonary hypertension by inhibiting pulmonary arterial smooth muscle cell pyroptosis via AMPK/NF-κB/NLRP3 Signaling. Int J Mol Sci, 2024; 25(15):8246; doi: 10.3390/ijms25158246
100.
HeZ, LiH, HanX, et al.Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice. Bone, 2020; 141:115573; doi: 10.1016/j.bone.2020.115573
101.
HechtJT, VeerisettyAC, WuJ, et al.Primary osteoarthritis early joint degeneration induced by endoplasmic reticulum stress is mitigated by resveratrol. Am J Pathol, 2021; 191(9):1624–1637; doi: 10.1016/j.ajpath.2021.05.016
102.
HerzigS, ShawRJ. AMPK: Guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol, 2018; 19(2):121–135; doi: 10.1038/nrm.2017.95
103.
HodgesPW, JamesG, BlomsterL, et al.Can proinflammatory cytokine gene expression explain multifidus muscle fiber changes after an intervertebral disc lesion? Spine (Phila Pa 1976), 2014; 39(13):1010–1017; doi: 10.1097/brs.0000000000000318
104.
HoffmanNJ, ParkerBL, ChaudhuriR, et al.Global phosphoproteomic analysis of human skeletal muscle reveals a network of exercise-regulated kinases and AMPK substrates. Cell Metab, 2015; 22(5):922–935; doi: 10.1016/j.cmet.2015.09.001
105.
HoldenMA, HattleM, RunhaarJ, et al.; OA Trial Bank Exercise Collaborative. Moderators of the effect of therapeutic exercise for knee and hip osteoarthritis: A systematic review and individual participant data meta-analysis. Lancet Rheumatol, 2023; 5(7):e386–e400; doi: 10.1016/s2665-9913(23)00122-4
106.
HonmaM, IkebuchiY, KariyaY, et al.Regulatory mechanisms of RANKL presentation to osteoclast precursors. Curr Osteoporos Rep, 2014; 12(1):115–120; doi: 10.1007/s11914-014-0189-0
107.
HoutkooperRH, PirinenE, AuwerxJ. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol, 2012; 13(4):225–238; doi: 10.1038/nrm3293
108.
HoweTE, SheaB, DawsonLJ, et al.Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev, 2011(7):Cd000333; doi: 10.1002/14651858.CD000333.pub2
109.
HuH, WangZ, YangH, et al.Hypoxic preconditional engineering small extracellular vesicles promoted intervertebral disc regeneration by activating Mir-7-5p/NF-Κb/Cxcl2 Axis. Adv Sci (Weinh), 2023; 10(35):e2304722; doi: 10.1002/advs.202304722
110.
HuL, XieX, XueH, et al.MiR-1224-5p modulates osteogenesis by coordinating osteoblast/osteoclast differentiation via the Rap1 signaling target ADCY2. Exp Mol Med, 2022; 54(7):961–972; doi: 10.1038/s12276-022-00799-9
111.
HuX, WangZ, WangW, et al.Irisin as an agent for protecting against osteoporosis: A review of the current mechanisms and pathways. J Adv Res, 2024; 62:175–186; doi: 10.1016/j.jare.2023.09.001
112.
HuangT, ChenX, HeJ, et al.Eugenol mimics exercise to promote skeletal muscle fiber remodeling and myokine IL-15 expression by activating TRPV1 channel. Elife, 2024; 12:RP90724; doi: 10.7554/eLife.90724
113.
HunterDJ, MarchL, ChewM. Osteoarthritis in 2020 and beyond: A Lancet Commission. Lancet, 2020; 396(10264):1711–1712; doi: 10.1016/s0140-6736(20)32230-3
114.
HusaM, PeturssonF, LotzM, et al.C/EBP homologous protein drives pro-catabolic responses in chondrocytes. Arthritis Res Ther, 2013; 15(6):R218; doi: 10.1186/ar4415
115.
HussainSA, MaroufBH, AliZS, et al.Efficacy and safety of co-administration of resveratrol with meloxicam in patients with knee osteoarthritis: A pilot interventional study. Clin Interv Aging, 2018; 13:1621–1630; doi: 10.2147/cia.S172758
116.
IskenderianA, LiuN, DengQ, et al.Myostatin and activin blockade by engineered follistatin results in hypertrophy and improves dystrophic pathology in mdx mouse more than myostatin blockade alone. Skelet Muscle, 2018; 8(1):34; doi: 10.1186/s13395-018-0180-z
117.
IwabuM, Okada-IwabuM, TanabeH, et al.AdipoR agonist increases insulin sensitivity and exercise endurance in AdipoR-humanized mice. Commun Biol, 2021; 4(1):45; doi: 10.1038/s42003-020-01579-9
118.
JiLL, YeoD, KangC, et al.The role of mitochondria in redox signaling of muscle homeostasis. J Sport Health Sci, 2020; 9(5):386–393; doi: 10.1016/j.jshs.2020.01.001
119.
JiML, JiangH, LiZ, et al.Sirt6 attenuates chondrocyte senescence and osteoarthritis progression. Nat Commun, 2022; 13(1):7658; doi: 10.1038/s41467-022-35424-w
120.
JiaS, YangY, BaiY, et al.Mechanical stimulation protects against chondrocyte pyroptosis through Irisin-induced suppression of PI3K/Akt/NF-κB signal pathway in osteoarthritis. Front Cell Dev Biol, 2022; 10:797855; doi: 10.3389/fcell.2022.797855
121.
JiaY, CuiR, WangC, et al.Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway. Redox Biol, 2020; 32:101534; doi: 10.1016/j.redox.2020.101534
122.
JiangA, XuP, YangZ, et al.Increased Sparc release from subchondral osteoblasts promotes articular chondrocyte degeneration under estrogen withdrawal. Osteoarthritis Cartilage, 2023; 31(1):26–38; doi: 10.1016/j.joca.2022.08.020
123.
JiangS, KimTM, ParkSY, et al.ROS-responsive MnO(2) mesoporous hydrogel to modulate liver-muscle crosstalk and mitigate NAFLD-associated sarcopenia via exosomal miR-582-5p delivery. Theranostics, 2025; 15(10):4579–4592; doi: 10.7150/thno.108280
124.
JiangW, LiuH, WanR, et al.Mechanisms linking mitochondrial mechanotransduction and chondrocyte biology in the pathogenesis of osteoarthritis. Ageing Res Rev, 2021; 67:101315; doi: 10.1016/j.arr.2021.101315
125.
JinH, ZhuY, WangXD, et al.BDNF corrects NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming through KLF2/HK1 pathway in vascular endothelial cells. Cell Signal, 2021; 78:109843; doi: 10.1016/j.cellsig.2020.109843
126.
JinL, Diaz-CanestroC, WangY, et al.Exerkines and cardiometabolic benefits of exercise: From bench to clinic. EMBO Mol Med, 2024; 16(3):432–444; doi: 10.1038/s44321-024-00027-z
127.
JonesRL, PaulL, SteultjensMPM, et al.Biomarkers associated with lower limb muscle function in individuals with sarcopenia: A systematic review. J Cachexia Sarcopenia Muscle, 2022; 13(6):2791–2806; doi: 10.1002/jcsm.13064
128.
KanazawaI, YamaguchiT, YanoS, et al.Activation of AMP kinase and inhibition of Rho kinase induce the mineralization of osteoblastic MC3T3-E1 cells through endothelial NOS and BMP-2 expression. Am J Physiol Endocrinol Metab, 2009; 296(1):E139–E146; doi: 10.1152/ajpendo.90677.2008
129.
KangMJ, MoonJW, LeeJO, et al.Metformin induces muscle atrophy by transcriptional regulation of myostatin via HDAC6 and FoxO3a. J Cachexia Sarcopenia Muscle, 2022; 13(1):605–620; doi: 10.1002/jcsm.12833
130.
KangX, QianJ, ShiYX, et al.Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis. Cell Stem Cell, 2024; 31(2):212–226.e217; doi: 10.1016/j.stem.2023.12.011
131.
KawamuraA, AoiW, AbeR, et al.Astaxanthin-, β-carotene-, and resveratrol-rich foods support resistance training-induced adaptation. Antioxidants (Basel), 2021; 10(1):113; doi: 10.3390/antiox10010113
132.
KawamuraK, FukumuraS, NikaidoK, et al.Resveratrol improves motor function in patients with muscular dystrophies: An open-label, single-arm, phase IIa study. Sci Rep, 2020; 10(1):20585; doi: 10.1038/s41598-020-77197-6
133.
KearnsAE, KhoslaS, KostenuikPJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev, 2008; 29(2):155–192; doi: 10.1210/er.2007-0014
134.
KerrHL, KrummK, AndersonB, et al.Mouse sarcopenia model reveals sex- and age-specific differences in phenotypic and molecular characteristics. J Clin Invest, 2024; 134(16):e172890; doi: 10.1172/jci172890
135.
KimY, LimJH, KimEN, et al.Adiponectin receptor agonist ameliorates cardiac lipotoxicity via enhancing ceramide metabolism in type 2 diabetic mice. Cell Death Dis, 2022; 13(3):282; doi: 10.1038/s41419-022-04726-8
136.
KimY, LimJH, KimMY, et al.The adiponectin receptor agonist adiporon ameliorates diabetic nephropathy in a model of type 2 diabetes. J Am Soc Nephrol, 2018; 29(4):1108–1127; doi: 10.1681/asn.2017060627
137.
KjøbstedR, TreebakJT, FentzJ, et al.Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner. Diabetes, 2015; 64(6):2042–2055; doi: 10.2337/db14-1402
138.
KloppenburgM. Inflammation is a relevant treatment target in osteoarthritis. Lancet, 2023; 402(10414):1725–1726; doi: 10.1016/s0140-6736(23)01726-9
139.
KongL, ZhangH, LuC, et al.AICAR, an AMP-activated protein kinase activator, ameliorates acute pancreatitis-associated liver injury partially through Nrf2-mediated antioxidant effects and inhibition of NLRP3 inflammasome activation. Front Pharmacol, 2021; 12:724514; doi: 10.3389/fphar.2021.724514
140.
KongX, YaoT, ZhouP, et al.Brown adipose tissue controls skeletal muscle function via the secretion of myostatin. Cell Metab, 2018; 28(4):631–643.e633; doi: 10.1016/j.cmet.2018.07.004
141.
KumagaiH, KimSJ, MillerB, et al.MOTS-c modulates skeletal muscle function by directly binding and activating CK2. iScience, 2024; 27(11):111212; doi: 10.1016/j.isci.2024.111212
142.
KumarR, NegiPS, SinghB, et al.Cordyceps sinensis promotes exercise endurance capacity of rats by activating skeletal muscle metabolic regulators. J Ethnopharmacol, 2011; 136(1):260–266; doi: 10.1016/j.jep.2011.04.040
143.
KurganN, StoikosJ, BaranowskiBJ, et al.Sclerostin influences exercise-induced adaptations in body composition and white adipose tissue morphology in male mice. J Bone Miner Res, 2023; 38(4):541–555; doi: 10.1002/jbmr.4768
144.
LatourteA, CherifiC, MailletJ, et al.Systemic inhibition of IL-6/Stat3 signalling protects against experimental osteoarthritis. Ann Rheum Dis, 2017; 76(4):748–755; doi: 10.1136/annrheumdis-2016-209757
145.
LawfordBJ, HallM, HinmanRS, et al.Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev, 2024; 12(12):Cd004376; doi: 10.1002/14651858.CD004376.pub4
146.
LeeC, ZengJ, DrewBG, et al.The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab, 2015; 21(3):443–454; doi: 10.1016/j.cmet.2015.02.009
147.
LeeJO, LeeSK, JungJH, et al.Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells. J Cell Physiol, 2011; 226(4):974–981; doi: 10.1002/jcp.22410
148.
LeeSJ. Myostatin: A skeletal muscle chalone. Annu Rev Physiol, 2023; 85:269–291; doi: 10.1146/annurev-physiol-012422-112116
149.
LeiS, LiuK, LiuC, et al.Cis-resveratrol blocks crystal-induced NLRP3 inflammasome activation via the TRPV4-Ca2+-phagocytosis-ROS axis. Phytomedicine, 2025; 146:157145; doi: 10.1016/j.phymed.2025.157145
150.
LiD, RuanG, ZhangY, et al.Metformin attenuates osteoarthritis by targeting chondrocytes, synovial macrophages and adipocytes. Rheumatology (Oxford), 2023; 62(4):1652–1661; doi: 10.1093/rheumatology/keac467
151.
LiF, ZhangF, ShiH, et al.Aerobic exercise suppresses CCN2 secretion from senescent muscle stem cells and boosts muscle regeneration in aged mice. J Cachexia Sarcopenia Muscle, 2024a;15(5):1733–1749; doi: 10.1002/jcsm.13526
152.
LiJ, HansenKC, ZhangY, et al.Rejuvenation of chondrogenic potential in a young stem cell microenvironment. Biomaterials, 2014; 35(2):642–653; doi: 10.1016/j.biomaterials.2013.09.099
153.
LiJ, ZhangB, LiuWX, et al.Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Ann Rheum Dis, 2020; 79(5):635–645; doi: 10.1136/annrheumdis-2019-216713
154.
LiK, LiY, MiJ, et al.Resveratrol protects against sodium nitroprusside induced nucleus pulposus cell apoptosis by scavenging ROS. Int J Mol Med, 2018; 41(5):2485–2492; doi: 10.3892/ijmm.2018.3461
155.
LiK, YangT, ChenF, et al.MOTS-c attenuates mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via an Nrf2-Dependent Mechanism. Free Radic Biol Med, 2025; 241:717–731; doi: 10.1016/j.freeradbiomed.2025.09.056
156.
LiL, YuM, LiY, et al.Synergistic anti-inflammatory and osteogenic n-HA/resveratrol/chitosan composite microspheres for osteoporotic bone regeneration. Bioact Mater, 2021a;6(5):1255–1266; doi: 10.1016/j.bioactmat.2020.10.018
157.
LiQ, GuoR, WuZ, et al.Endplate chondrocyte-derived exosomal miR-128-3p mitigates intervertebral disc degeneration by targeting TRAF6 via the miR-128-3p/TRAF6 axis to suppress pyroptosis. Int Immunopharmacol, 2024b;143(Pt 3):113620; doi: 10.1016/j.intimp.2024.113620
158.
LiX, PhillipsFM, AnHS, et al.The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc. Spine (Phila Pa 1976), 2008; 33(24):2586–2595; doi: 10.1097/BRS.0b013e3181883883
159.
LiX, ZhuX, WuH, et al.Roles and mechanisms of Irisin in attenuating pathological features of osteoarthritis. Front Cell Dev Biol, 2021b;9:703670; doi: 10.3389/fcell.2021.703670
160.
LiZ, HuangZ, ZhangH, et al.Moderate-intensity exercise alleviates pyroptosis by promoting autophagy in osteoarthritis via the P2X7/AMPK/mTOR axis. Cell Death Discov, 2021c;7(1):346; doi: 10.1038/s41420-021-00746-z
161.
LiZ, TangY, WangL, et al.Tetrahedral framework nucleic acids-based delivery of microRNA-155 alleviates intervertebral disc degeneration through targeting Bcl-2/Bax apoptosis pathway. Cell Prolif, 2024c;57(11):e13689; doi: 10.1111/cpr.13689
162.
LiangQ, WangXP, ChenTS. Resveratrol protects rabbit articular chondrocyte against sodium nitroprusside-induced apoptosis via scavenging ROS. Apoptosis, 2014; 19(9):1354–1363; doi: 10.1007/s10495-014-1012-1
163.
LiaoZ, LiS, LuS, et al.Metformin facilitates mesenchymal stem cell-derived extracellular nanovesicles release and optimizes therapeutic efficacy in intervertebral disc degeneration. Biomaterials, 2021; 274:120850; doi: 10.1016/j.biomaterials.2021.120850
164.
LiaoZY, ChenJL, XiaoMH, et al.The effect of exercise, resveratrol or their combination on Sarcopenia in aged rats via regulation of AMPK/Sirt1 pathway. Exp Gerontol, 2017; 98:177–183; doi: 10.1016/j.exger.2017.08.032
165.
LimJH, AhmadSS, HwangYC, et al.The effects of laxogenin and 5-alpha-hydroxy-laxogenin on myotube formation and maturation during cultured meat production. Int J Mol Sci, 2025; 26(1):345; doi: 10.3390/ijms26010345
166.
LimYZ, WangY, EsteeM, et al.Metformin as a potential disease-modifying drug in osteoarthritis: A systematic review of pre-clinical and human studies. Osteoarthritis Cartilage, 2022; 30(11):1434–1442; doi: 10.1016/j.joca.2022.05.005
167.
LinC, JiangX, DaiZ, et al.Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res, 2009; 24(10):1651–1661; doi: 10.1359/jbmr.090411
168.
LinF, ChenJ, ChenM, et al.Protective effect and possible mechanisms of resveratrol in animal models of osteoporosis: A preclinical systematic review and meta-analysis. Phytother Res, 2023a;37(11):5223–5242; doi: 10.1002/ptr.7954
169.
LinJ, ZhugeJ, ZhengX, et al.Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration via the AMPK signaling pathway. Free Radic Biol Med, 2020; 150:109–119; doi: 10.1016/j.freeradbiomed.2020.02.024
170.
LinTC, LinJN, YangIH, et al.The combination of resveratrol and Bletilla striata polysaccharide decreases inflammatory markers of early osteoarthritis knee and the preliminary results on LPS-induced OA rats. Bioeng Transl Med, 2023b;8(4):e10431; doi: 10.1002/btm2.10431
171.
LinY, YangRY, LiJ, et al.MOTS-c-modified functional self-assembly peptide hydrogels enhance the activity of nucleus pulposus-derived mesenchymal stem cells of intervertebral disc degeneration. Mater Today Bio, 2025; 32:101872; doi: 10.1016/j.mtbio.2025.101872
172.
LisiewskiLE, JacobsenHE, ViolaDCM, et al.Intradiscal inflammatory stimulation induces spinal pain behavior and intervertebral disc degeneration in vivo. Faseb J, 2024; 38(1):e23364; doi: 10.1096/fj.202300227R
173.
LiuB, GouY, TsuzukiT, et al.d-allulose improves endurance and recovery from exhaustion in male C57BL/6J Mice. Nutrients, 2022; 14(3):404; doi: 10.3390/nu14030404
174.
LiuB, XuJ, LuL, et al.Metformin induces pyroptosis in leptin receptor-defective hepatocytes via overactivation of the AMPK axis. Cell Death Dis, 2023a;14(2):82; doi: 10.1038/s41419-023-05623-4
175.
LiuD, WangS, LiuS, et al.Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies. Mol Aspects Med, 2024; 97:101270; doi: 10.1016/j.mam.2024.101270
176.
LiuH, LiuS, JiH, et al.An adiponectin receptor agonist promote osteogenesis via regulating bone-fat balance. Cell Prolif, 2021; 54(6):e13035; doi: 10.1111/cpr.13035
177.
LiuH, ZhaoQ, LiuS, et al.Aging alters the effect of adiponectin receptor signaling on bone marrow-derived mesenchymal stem cells. Aging Cell, 2025; 24(2):e14390; doi: 10.1111/acel.14390
178.
LiuJ, JiaS, YangY, et al.Exercise induced meteorin-like protects chondrocytes against inflammation and pyroptosis in osteoarthritis by inhibiting PI3K/Akt/NF-κB and NLRP3/caspase-1/GSDMD signaling. Biomed Pharmacother, 2023b;158:114118; doi: 10.1016/j.biopha.2022.114118
179.
LiuX, GuoQ, WangL, et al.Metformin attenuates high-fat diet induced metabolic syndrome related osteoarthritis through inhibition of prostaglandins. Front Cell Dev Biol, 2023c;11:1184524; doi: 10.3389/fcell.2023.1184524
180.
LiuY, XueM, HanY, et al.Exosomes from M2c macrophages alleviate intervertebral disc degeneration by promoting synthesis of the extracellular matrix via MiR-124/CILP/TGF-β. Bioeng Transl Med, 2023d;8(6):e10500; doi: 10.1002/btm2.10500
181.
Lo VersoF, CarnioS, VainshteinA, et al.Autophagy is not required to sustain exercise and PRKAA1/AMPK activity but is important to prevent mitochondrial damage during physical activity. Autophagy, 2014; 10(11):1883–1894; doi: 10.4161/auto.32154
182.
LohbergerB, KalteneggerH, WeiglL, et al.Mechanical exposure and diacerein treatment modulates integrin-FAK-MAPKs mechanotransduction in human osteoarthritis chondrocytes. Cell Signal, 2019; 56:23–30; doi: 10.1016/j.cellsig.2018.12.010
183.
LongY, WuY, ZhongY, et al.Resveratrol as a potential therapeutic agent for sarcopenic obesity: Insights from in vivoperiments. Biomed Pharmacother, 2024; 179:117396; doi: 10.1016/j.biopha.2024.117396
184.
LouC, JiangH, LinZ, et al.MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6. J Nanobiotechnology, 2023; 21(1):486; doi: 10.1186/s12951-023-02264-9
185.
LuH, FanL, ZhangW, et al.The mitochondrial genome-encoded peptide MOTS-c interacts with Bcl-2 to alleviate nonalcoholic steatohepatitis progression. Cell Rep, 2024; 43(1):113587; doi: 10.1016/j.celrep.2023.113587
186.
LuH, JiaC, WuD, et al.Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway. Cell Death Dis, 2021; 12(10):865; doi: 10.1038/s41419-021-04157-x
187.
LuW, DingZ, LiuF, et al.Dopamine delays articular cartilage degradation in osteoarthritis by negative regulation of the NF-κB and JAK2/STAT3 signaling pathways. Biomed Pharmacother, 2019; 119:109419; doi: 10.1016/j.biopha.2019.109419
188.
LuanP, D’AmicoD, AndreuxPA, et al.Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy. Sci Transl Med, 2021; 13(588):eabb0319; doi: 10.1126/scitranslmed.abb0319
189.
LuanS, WanQ, LuoH, et al.Running exercise alleviates pain and promotes cell proliferation in a rat model of intervertebral disc degeneration. Int J Mol Sci, 2015; 16(1):2130–2144; doi: 10.3390/ijms16012130
190.
LvYJ, YangY, SuiBD, et al.Resveratrol counteracts bone loss via mitofilin-mediated osteogenic improvement of mesenchymal stem cells in senescence-accelerated mice. Theranostics, 2018; 8(9):2387–2406; doi: 10.7150/thno.23620
191.
Mairet-CoelloG, CourchetJ, PierautS, et al.The CAMKK2-AMPK kinase pathway mediates the synaptotoxic effects of Aβ oligomers through Tau phosphorylation. Neuron, 2013; 78(1):94–108; doi: 10.1016/j.neuron.2013.02.003
192.
MakRH, CheungWW. MicroRNA as novel exercise mimetic for muscle wasting in CKD. J Am Soc Nephrol, 2017; 28(9):2557–2559; doi: 10.1681/asn.2017060631
193.
MalinSK, GerberR, ChipkinSR, et al.Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care, 2012; 35(1):131–136; doi: 10.2337/dc11-0925
194.
ManiscalcoE, AbbadessaG, GiordanoM, et al.Metformin regulates myoblast differentiation through an AMPK-dependent mechanism. PLoS One, 2023; 18(2):e0281718; doi: 10.1371/journal.pone.0281718
195.
MaoMZ, ZhengMH, GuoB, et al.FNDC5/irisin-enriched sEVs conjugated with bone-targeting aptamer alleviate osteoporosis: A potential alternative to exercise. J Nanobiotechnology, 2025a;23(1):504; doi: 10.1186/s12951-025-03587-5
196.
MaoX, LeiH, YiT, et al.Lipid reprogramming induced by the TFEB-ERRα axis enhanced membrane fluidity to promote EC progression. J Exp Clin Cancer Res, 2022; 41(1):28; doi: 10.1186/s13046-021-02211-2
197.
MaoX, LvK, QiW, et al.Research progress on sarcopenia in the musculoskeletal system. Bone Res, 2025b;13(1):78; doi: 10.1038/s41413-025-00455-8
198.
MaoY, XuW, XieZ, et al.Association of Irisin and CRP levels with the radiographic severity of knee osteoarthritis. Genet Test Mol Biomarkers, 2016; 20(2):86–89; doi: 10.1089/gtmb.2015.0170
199.
MarascoMR, ContehAM, ReissausCA, et al.Interleukin-6 reduces β-cell oxidative stress by linking autophagy with the antioxidant response. Diabetes, 2018; 67(8):1576–1588; doi: 10.2337/db17-1280
200.
Martin GilC, RaoofR, VersteegS, et al.Myostatin and CXCL11 promote nervous tissue macrophages to maintain osteoarthritis pain. Brain Behav Immun, 2024; 116:203–215; doi: 10.1016/j.bbi.2023.12.004
201.
MartinLM, MöllerM, WeissU, et al.5-Amino-1-β-D-Ribofuranosyl-Imidazole-4-Carboxamide (AICAR) reduces peripheral inflammation by macrophage phenotype shift. Int J Mol Sci, 2019; 20(13):3255; doi: 10.3390/ijms20133255
202.
Martinez-CantonM, Galvan-AlvarezV, Garcia-GonzalezE, et al.A mango leaf extract (Zynamite(®)) combined with quercetin has exercise-mimetic properties in human skeletal muscle. Nutrients, 2023; 15(13):2848; doi: 10.3390/nu15132848
203.
MassartIS, KouakouAN, PeletN, et al.Administration of adiponectin receptor agonist AdipoRon relieves cancer cachexia by mitigating inflammation in tumour-bearing mice. J Cachexia Sarcopenia Muscle, 2024; 15(3):919–933; doi: 10.1002/jcsm.13454
204.
Mayeuf-LouchartA, ThorelQ, DelhayeS, et al.Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass. Sci Rep, 2017; 7(1):14383; doi: 10.1038/s41598-017-14596-2
205.
MengJ, LvZ, SunC, et al.An extract of Lycium barbarum mimics exercise to improve muscle endurance through increasing type IIa oxidative muscle fibers by activating ERRγ. Faseb J, 2020; 34(9):11460–11473; doi: 10.1096/fj.202000136R
206.
MengW, MengX, HanC, et al.BDNF improves fracture healing through promoting osteoblasts proliferation and migration via trkb/akt regulated NUCKS1 expression. Sci Rep, 2025; 15(1):27107; doi: 10.1038/s41598-025-11594-7
207.
MerckenEM, CarboneauBA, Krzysik-WalkerSM, et al.Of mice and men: The benefits of caloric restriction, exercise, and mimetics. Ageing Res Rev, 2012; 11(3):390–398; doi: 10.1016/j.arr.2011.11.005
208.
MisquittaNS, Ravel-ChapuisA, JasminBJ. Combinatorial treatment with exercise and AICAR potentiates the rescue of myotonic dystrophy type 1 mouse muscles in a sex-specific manner. Hum Mol Genet, 2023; 32(4):551–566; doi: 10.1093/hmg/ddac222
209.
MixKS, AtturMG, Al-MussawirH, et al.Transcriptional repression of matrix metalloproteinase gene expression by the orphan nuclear receptor NURR1 in cartilage. J Biol Chem, 2007; 282(13):9492–9504; doi: 10.1074/jbc.M608327200
210.
MolinariF, PinF, GoriniS, et al.The mitochondrial metabolic reprogramming agent trimetazidine as an ‘exercise mimetic’ in cachectic C26-bearing mice. J Cachexia Sarcopenia Muscle, 2017; 8(6):954–973; doi: 10.1002/jcsm.12226
211.
MoonHY, BeckeA, BerronD, et al.Running-induced systemic cathepsin b secretion is associated with memory function. Cell Metab, 2016; 24(2):332–340; doi: 10.1016/j.cmet.2016.05.025
212.
MoonMH, JeongJK, LeeYJ, et al.SIRT1, a class III histone deacetylase, regulates TNF-α-induced inflammation in human chondrocytes. Osteoarthritis Cartilage, 2013; 21(3):470–480; doi: 10.1016/j.joca.2012.11.017
213.
MoonYJ, ZhangZ, BangIH, et al.Sirtuin 6 in preosteoclasts suppresses age- and estrogen deficiency-related bone loss by stabilizing estrogen receptor α. Cell Death Differ, 2019; 26(11):2358–2370; doi: 10.1038/s41418-019-0306-9
214.
MuW, WangZ, MaC, et al.Metformin promotes the proliferation and differentiation of murine preosteoblast by regulating the expression of sirt6 and oct4. Pharmacol Res, 2018; 129:462–474; doi: 10.1016/j.phrs.2017.11.020
215.
MuraseT, HaramizuS, OtaN, et al.Suppression of the aging-associated decline in physical performance by a combination of resveratrol intake and habitual exercise in senescence-accelerated mice. Biogerontology, 2009; 10(4):423–434; doi: 10.1007/s10522-008-9177-z
216.
MyersRW, GuanHP, EhrhartJ, et al.Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy. Science, 2017; 357(6350):507–511; doi: 10.1126/science.aah5582
217.
NaHS, KwonJY, LeeSY, et al.Metformin attenuates monosodium-iodoacetate-induced osteoarthritis via regulation of pain mediators and the autophagy-lysosomal pathway. Cells, 2021; 10(3):681; doi: 10.3390/cells10030681
218.
NagaiK, MatsushitaT, MatsuzakiT, et al.Depletion of SIRT6 causes cellular senescence, DNA damage, and telomere dysfunction in human chondrocytes. Osteoarthritis Cartilage, 2015; 23(8):1412–1420; doi: 10.1016/j.joca.2015.03.024
219.
NarkarVA, DownesM, YuRT, et al.AMPK and PPARdelta agonists are exercise mimetics. Cell, 2008; 134(3):405–415; doi: 10.1016/j.cell.2008.06.051
220.
National Collaborating Centre for Chronic. National Institute for Health and Clinical Excellence: Guidance. In: Osteoarthritis: National Clinical Guideline for Care and Management in Adults. Royal College of Physicians of London: London; 2008.
221.
NegmAM, LeeJ, HamidianR, et al.Management of sarcopenia: A network meta-analysis of randomized controlled trials. J Am Med Dir Assoc, 2022; 23(5):707–714; doi: 10.1016/j.jamda.2022.01.057
222.
NegroM, PernaS, SpadacciniD, et al.Effects of 12 Weeks of Essential Amino Acids (EAA)-based multi-ingredient nutritional supplementation on muscle mass, muscle strength, muscle power and fatigue in healthy elderly subjects: A randomized controlled double-blind study. J Nutr Health Aging, 2019; 23(5):414–424; doi: 10.1007/s12603-019-1163-4
223.
NelliganRK, HinmanRS, KaszaJ, et al.Effects of a self-directed web-based strengthening exercise and physical activity program supported by automated text messages for people with knee osteoarthritis: A randomized clinical trial. JAMA Intern Med, 2021; 181(6):776–785; doi: 10.1001/jamainternmed.2021.0991
224.
NetoIVS, PintoAP, MuñozVR, et al.Pleiotropic and multi-systemic actions of physical exercise on PGC-1α signaling during the aging process. Ageing Res Rev, 2023; 87:101935; doi: 10.1016/j.arr.2023.101935
225.
NguyenC, CoudeyreE, BoutronI, et al.Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL). PLoS Med, 2024; 21(8):e1004440; doi: 10.1371/journal.pmed.1004440
226.
NicolasS, RochetN, GautierN, et al.The adiponectin receptor agonist AdipoRon normalizes glucose metabolism and prevents obesity but not growth retardation induced by glucocorticoids in young mice. Metabolism, 2020; 103:154027; doi: 10.1016/j.metabol.2019.154027
227.
NirmalaFS, LeeH, KimYI, et al.Exercise-induced signaling activation by Chrysanthemum zawadskii and its active compound, linarin, ameliorates age-related sarcopenia through Sestrin 1 regulation. Phytomedicine, 2024; 129:155695; doi: 10.1016/j.phymed.2024.155695
228.
NiuW, WangH, WangB, et al.Resveratrol improves muscle regeneration in obese mice through enhancing mitochondrial biogenesis. J Nutr Biochem, 2021; 98:108804; doi: 10.1016/j.jnutbio.2021.108804
229.
NoehrenB, KosmacK, WaltonRG, et al.Alterations in quadriceps muscle cellular and molecular properties in adults with moderate knee osteoarthritis. Osteoarthritis Cartilage, 2018; 26(10):1359–1368; doi: 10.1016/j.joca.2018.05.011
230.
NoguchiI, MaedaH, KobayashiK, et al.Carbon monoxide-loaded cell therapy as an exercise mimetic for sarcopenia treatment. Free Radic Biol Med, 2024; 220:67–77; doi: 10.1016/j.freeradbiomed.2024.04.231
231.
NordklintAK, AlmdalTP, VestergaardP, et al.Effect of metformin and insulin vs. placebo and insulin on whole body composition in overweight patients with type 2 diabetes: A randomized placebo-controlled trial. Osteoporos Int, 2021; 32(9):1837–1848; doi: 10.1007/s00198-021-05870-1
232.
OhnishiH, ZhangZ, YurubeT, et al.Anti-inflammatory effects of adiponectin receptor agonist adiporon against intervertebral disc degeneration. Int J Mol Sci, 2023; 24(10):8566; doi: 10.3390/ijms24108566
233.
Okada-IwabuM, YamauchiT, IwabuM, et al.A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature, 2013; 503(7477):493–499; doi: 10.1038/nature12656
234.
OnoT, DendaR, TsukaharaY, et al.Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1α signaling. Bone Res, 2022; 10(1):52; doi: 10.1038/s41413-022-00225-w
OrnstrupMJ, HarsløfT, KjærTN, et al.Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: A randomized placebo-controlled trial. J Clin Endocrinol Metab, 2014; 99(12):4720–4729; doi: 10.1210/jc.2014-2799
237.
OzciviciE, LuuYK, AdlerB, et al.Mechanical signals as anabolic agents in bone. Nat Rev Rheumatol, 2010; 6(1):50–59; doi: 10.1038/nrrheum.2009.239
238.
PanC, YangY, ZhaoZ, et al.Combined effects of natural products and exercise on apoptosis pathways in obesity-related skeletal muscle dysfunction. Apoptosis, 2025a;30(3–4):537–552; doi: 10.1007/s10495-024-02069-7
239.
PanF, WangY, LimYZ, et al.Metformin for knee osteoarthritis in patients with overweight or obesity: A randomized clinical trial. JAMA, 2025b;333(20):1804–1812; doi: 10.1001/jama.2025.3471
240.
PangBPS, IuECY, HangM, et al.Deficiency of muscle-generated brain-derived neurotrophic factor causes inflammatory myopathy through reactive oxygen species-mediated necroptosis and pyroptosis. Redox Biol, 2024; 78:103418; doi: 10.1016/j.redox.2024.103418
241.
ParkEJ, TruongVL, JeongWS, et al.Brain-Derived Neurotrophic Factor (BDNF) enhances osteogenesis and may improve bone microarchitecture in an ovariectomized rat model. Cells, 2024; 13(6):518; doi: 10.3390/cells13060518
242.
PedersenBK, FebbraioMA. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat Rev Endocrinol, 2012; 8(8):457–465; doi: 10.1038/nrendo.2012.49
243.
PetrocelliJJ, McKenzieAI, de HartN, et al.Disuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment. Aging Cell, 2023; 22(11):e13936; doi: 10.1111/acel.13936
244.
PeturssonF, HusaM, JuneR, et al.Linked decreases in liver kinase B1 and AMP-activated protein kinase activity modulate matrix catabolic responses to biomechanical injury in chondrocytes. Arthritis Res Ther, 2013; 15(4):R77; doi: 10.1186/ar4254
245.
PiccaA, Coelho-JuniorHJ, CalvaniR, et al.Biomarkers shared by frailty and sarcopenia in older adults: A systematic review and meta-analysis. Ageing Res Rev, 2022; 73:101530; doi: 10.1016/j.arr.2021.101530
246.
PrattJ, MotanovaE, NariciMV, et al.Plasma brain-derived neurotrophic factor concentrations are elevated in community-dwelling adults with sarcopenia. Age Ageing, 2025; 54(2):afaf024; doi: 10.1093/ageing/afaf024
247.
PurmessurD, FreemontAJ, HoylandJA. Expression and regulation of neurotrophins in the nondegenerate and degenerate human intervertebral disc. Arthritis Res Ther, 2008; 10(4):R99; doi: 10.1186/ar2487
248.
PuthoffML, JanzKF, NielsonD. The relationship between lower extremity strength and power to everday walking behaviors in older adults with functional limitations. J Geriatr Phys Ther, 2008; 31(1):24–31; doi: 10.1519/00139143-200831010-00005
249.
QaisarR, KarimA, MuhammadT, et al.Metformin improves sarcopenia-related quality of life in geriatric adults: A randomized controlled trial. Arch Med Res, 2024; 55(4):102998; doi: 10.1016/j.arcmed.2024.102998
250.
QinL, YangJ, SuX, et al.The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype. Genes Dis, 2023; 10(3):1114–1129; doi: 10.1016/j.gendis.2022.09.010
251.
QinN, WeiL, LiW, et al.Local intra-articular injection of resveratrol delays cartilage degeneration in C57BL/6 mice by inducing autophagy via AMPK/mTOR pathway. J Pharmacol Sci, 2017; 134(3):166–174; doi: 10.1016/j.jphs.2017.06.002
252.
QinT, ShiM, ZhangC, et al.The muscle-intervertebral disc interaction mediated by L-BAIBA modulates extracellular matrix homeostasis and PANoptosis in nucleus pulposus cells. Exp Mol Med, 2024; 56(11):2503–2518; doi: 10.1038/s12276-024-01345-5
253.
QiuWJ, XuMZ, ZhuXD, et al.MicroRNA-27a alleviates IL-1β-induced inflammatory response and articular cartilage degradation via TLR4/NF-κB signaling pathway in articular chondrocytes. Int Immunopharmacol, 2019; 76:105839; doi: 10.1016/j.intimp.2019.105839
254.
QuB, ZengZ, YangH, et al.Resveratrol reversed rosiglitazone administration induced bone loss in rats with type 2 diabetes mellitus. Biomed Pharmacother, 2024; 178:117208; doi: 10.1016/j.biopha.2024.117208
255.
QuickeJG, ConaghanPG, CorpN, et al.Osteoarthritis year in review 2021: Epidemiology & therapy. Osteoarthritis Cartilage, 2022; 30(2):196–206; doi: 10.1016/j.joca.2021.10.003
256.
RenLR, YaoRB, WangSY, et al.MiR-27a-3p promotes the osteogenic differentiation by activating CRY2/ERK1/2 axis. Mol Med, 2021; 27(1):43; doi: 10.1186/s10020-021-00303-5
257.
ReynoldsT, MillsN, HoyteD, et al.The oldest of old male C57B/6J mice are protected from sarcopenic obesity: The possible role of skeletal muscle protein kinase B expression. Int J Mol Sci, 2024; 25(19):10278; doi: 10.3390/ijms251910278
258.
RogeriPS, ZanellaRJr, MartinsGL, et al.Strategies to prevent sarcopenia in the aging process: Role of protein intake and exercise. Nutrients, 2021; 14(1):52; doi: 10.3390/nu14010052
259.
RuasJL, WhiteJP, RaoRR, et al.A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell, 2012; 151(6):1319–1331; doi: 10.1016/j.cell.2012.10.050
260.
RybalkaE, TimpaniCA, DebruinDA, et al.The failed clinical story of myostatin inhibitors against duchenne muscular dystrophy: Exploring the biology behind the battle. Cells, 2020; 9(12):2657; doi: 10.3390/cells9122657
261.
SaadFA. Novel insights into the complex architecture of osteoporosis molecular genetics. Ann N Y Acad Sci, 2020; 1462(1):37–52; doi: 10.1111/nyas.14231
262.
Sáez de AsteasuML, Martínez-VelillaN, Zambom-FerraresiF, et al.Short-term multicomponent exercise impact on muscle function and structure in hospitalized older at risk of acute sarcopenia. J Cachexia Sarcopenia Muscle, 2024; 15(6):2586–2594; doi: 10.1002/jcsm.13602
263.
SafiriS, KolahiAA, CrossM, et al.Prevalence, deaths, and disability-adjusted life years due to musculoskeletal disorders for 195 countries and territories 1990-2017. Arthritis Rheumatol, 2021; 73(4):702–714; doi: 10.1002/art.41571
264.
SatoR, VaticM, Peixoto da FonsecaGW, et al.Biological basis and treatment of frailty and sarcopenia. Cardiovasc Res, 2024; 120(9):982–998; doi: 10.1093/cvr/cvae073
ScarpullaRC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev, 2008; 88(2):611–638; doi: 10.1152/physrev.00025.2007
267.
SchwartzAV, PanQ, ArodaVR, et al.; Diabetes Prevention Program Research Group. Long-term effects of lifestyle and metformin interventions in DPP on bone density. Osteoporos Int, 2021; 32(11):2279–2287; doi: 10.1007/s00198-021-05989-1
268.
SelvaisCM, Davis-López de CarrizosaMA, NachitM, et al.AdipoRon enhances healthspan in middle-aged obese mice: Striking alleviation of myosteatosis and muscle degenerative markers. J Cachexia Sarcopenia Muscle, 2023; 14(1):464–478; doi: 10.1002/jcsm.13148
269.
SelvaisCM, Davis-López de CarrizosaMA, VerseleR, et al.Challenging sarcopenia: Exploring adiporon in aging skeletal muscle as a healthspan-extending shield. Antioxidants (Basel), 2024; 13(9):1073; doi: 10.3390/antiox13091073
270.
ShenY, ShiQ, NongK, et al.Exercise for sarcopenia in older people: A systematic review and network meta-analysis. J Cachexia Sarcopenia Muscle, 2023; 14(3):1199–1211; doi: 10.1002/jcsm.13225
271.
SheroJA, LindholmME, SandriM, et al.Skeletal muscle as a mediator of interorgan crosstalk during exercise: Implications for aging and obesity. Circ Res, 2025; 136(11):1407–1432; doi: 10.1161/circresaha.124.325614
272.
ShiJ, ChenL, WangX, et al.SIRT6 inhibits endoplasmic reticulum stress-mediated ferroptosis by activating Nrf2/HO-1 signaling to alleviate osteoarthritis. Inflamm Res, 2025; 74(1):35; doi: 10.1007/s00011-025-01998-6
273.
ShinHE, JangJY, JungH, et al.MicroRNAs as commonly expressed biomarkers for sarcopenia and frailty: A systematic review. Exp Gerontol, 2024; 197:112600; doi: 10.1016/j.exger.2024.112600
274.
ShinHE, WonCW, DuqueG, et al.Circulating miR-144-3p as a novel independent biomarker associated with low muscle strength among older adults. J Cachexia Sarcopenia Muscle, 2025; 16(4):e70026; doi: 10.1002/jcsm.70026
275.
ShuD, DaiS, WangJ, et al.Impact of running exercise on intervertebral disc: A systematic review. Sports Health, 2024; 16(6):958–970; doi: 10.1177/19417381231221125
276.
SiM, ChenJ, YuR, et al.Protein kinase ROCK1 activates mitochondrial fission linking to oxidative stress and muscle atrophy. Kidney Int, 2025; 108(4):626–641; doi: 10.1016/j.kint.2025.05.019
277.
SinghA, D’AmicoD, AndreuxPA, et al.Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Rep Med, 2022; 3(5):100633; doi: 10.1016/j.xcrm.2022.100633
278.
SiragoG, TonioloL, CreaE, et al.A short-term treatment with resveratrol improves the inflammatory conditions of Middle-aged mice skeletal muscles. Int J Food Sci Nutr, 2022; 73(5):630–637; doi: 10.1080/09637486.2022.2027889
279.
SongMY, HanCY, MoonYJ, et al.Sirt6 reprograms myofibers to oxidative type through CREB-dependent Sox6 suppression. Nat Commun, 2022a;13(1):1808; doi: 10.1038/s41467-022-29472-5
280.
SongP, ChenT, RuiS, et al.Canagliflozin promotes osteoblastic MC3T3-E1 differentiation via AMPK/RUNX2 and improves bone microarchitecture in type 2 diabetic mice. Front Endocrinol (Lausanne), 2022b;13:1081039; doi: 10.3389/fendo.2022.1081039
281.
SpauldingHR, YanZ. AMPK and the adaptation to exercise. Annu Rev Physiol, 2022; 84:209–227; doi: 10.1146/annurev-physiol-060721-095517
282.
SriramS, SubramanianS, SathiakumarD, et al.Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF-κB. Aging Cell, 2011; 10(6):931–948; doi: 10.1111/j.1474-9726.2011.00734.x
283.
SteeleJ, Bruce-LowS, SmithD, et al.Can specific loading through exercise impart healing or regeneration of the intervertebral disc? Spine J, 2015; 15(10):2117–2121; doi: 10.1016/j.spinee.2014.08.446
284.
StorlinoG, ColaianniG, SanesiL, et al.Irisin prevents disuse-induced osteocyte apoptosis. J Bone Miner Res, 2020; 35(4):766–775; doi: 10.1002/jbmr.3944
285.
SuY, SuZ. Impact of exercise on immune cell infiltration in muscle tissue: Implications for muscle repair and chronic disease. Clin Exp Med, 2025; 25(1):306; doi: 10.1007/s10238-025-01852-3
286.
SunK, JingX, GuoJ, et al.Mitophagy in degenerative joint diseases. Autophagy, 2021; 17(9):2082–2092; doi: 10.1080/15548627.2020.1822097
287.
TangJ, LiuT, WenX, et al.Estrogen-related receptors: Novel potential regulators of osteoarthritis pathogenesis. Mol Med, 2021; 27(1):5; doi: 10.1186/s10020-021-00270-x
288.
TaoH, LiW, ZhangW, et al.Urolithin A suppresses RANKL-induced osteoclastogenesis and postmenopausal osteoporosis by, suppresses inflammation and downstream NF-κB activated pyroptosis pathways. Pharmacol Res, 2021; 174:105967; doi: 10.1016/j.phrs.2021.105967
289.
TaoL, WangJ, WangK, et al.Exerkine FNDC5/irisin-enriched exosomes promote proliferation and inhibit ferroptosis of osteoblasts through interaction with Caveolin-1. Aging Cell, 2024; 23(8):e14181; doi: 10.1111/acel.14181
290.
TaoSC, YuanT, ZhangYL, et al.Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics, 2017; 7(1):180–195; doi: 10.7150/thno.17133
291.
TezzeC, AmendolagineFI, NogaraL, et al.A combination of metformin and galantamine exhibits synergistic benefits in the treatment of sarcopenia. JCI Insight, 2023; 8(15):e168787; doi: 10.1172/jci.insight.168787
292.
Thaung ZawJJ, HowePRC, WongRHX. Long-term resveratrol supplementation improves pain perception, menopausal symptoms, and overall well-being in postmenopausal women: Findings from a 24-month randomized, controlled, crossover trial. Menopause, 2020; 28(1):40–49; doi: 10.1097/gme.0000000000001643
293.
TongX, ZhangC, WangD, et al.Suppression of AMP-activated protein kinase reverses osteoprotegerin-induced inhibition of osteoclast differentiation by reducing autophagy. Cell Prolif, 2020; 53(1):e12714; doi: 10.1111/cpr.12714
294.
UngurianuA, ZanfirescuA, MarginăD. Sirtuins, resveratrol and the intertwining cellular pathways connecting them. Ageing Res Rev, 2023; 88:101936; doi: 10.1016/j.arr.2023.101936
295.
UthmanOA, van der WindtDA, JordanJL, et al.Exercise for lower limb osteoarthritis: Systematic review incorporating trial sequential analysis and network meta-analysis. Bmj, 2013; 347:f5555; doi: 10.1136/bmj.f5555
296.
VarahraA, RodriguesIB, MacDermidJC, et al.Exercise to improve functional outcomes in persons with osteoporosis: A systematic review and meta-analysis. Osteoporos Int, 2018; 29(2):265–286; doi: 10.1007/s00198-017-4339-y
297.
VilchinskayaNA, RozhkovSV, TurtikovaOV, et al.AMPK phosphorylation impacts apoptosis in differentiating myoblasts isolated from atrophied rat soleus muscle. Cells, 2023; 12(6):920; doi: 10.3390/cells12060920
298.
ViñaJ, Gomez-CabreraMC, BorrasC, et al.Mitochondrial biogenesis in exercise and in ageing. Adv Drug Deliv Rev, 2009; 61(14):1369–1374; doi: 10.1016/j.addr.2009.06.006
299.
von WaldenF, Fernandez-GonzaloR, NorrbomJ, et al.Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol (1985), 2021; 131(3):1035–1042; doi: 10.1152/japplphysiol.00706.2019
300.
WagnerKR. The elusive promise of myostatin inhibition for muscular dystrophy. Curr Opin Neurol, 2020; 33(5):621–628; doi: 10.1097/wco.0000000000000853
301.
WangB, ShiY, ChenJ, et al.High glucose suppresses autophagy through the AMPK pathway while it induces autophagy via oxidative stress in chondrocytes. Cell Death Dis, 2021; 12(6):506; doi: 10.1038/s41419-021-03791-9
302.
WangB, ZhangC, ZhangA, et al.MicroRNA-23a and MicroRNA-27a mimic exercise by ameliorating CKD-induced muscle atrophy. J Am Soc Nephrol, 2017a;28(9):2631–2640; doi: 10.1681/asn.2016111213
303.
WangC, ChenWG, ChenH, et al.Exercise improves hypobaric hypoxia-induced skeletal muscle dysfunction via Sirt1-Mediated myotube and mitochondrial remodeling. J Adv Res, 2025a:S2090; doi: 10.1016/j.jare.2025.08.022
304.
WangFS, KuoCW, KoJY, et al.Irisin mitigates oxidative stress, chondrocyte dysfunction and osteoarthritis development through regulating mitochondrial integrity and autophagy. Antioxidants (Basel), 2020a;9(9):810; doi: 10.3390/antiox9090810
305.
WangG, WangY, YangQ, et al.Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Cell Death Dis, 2022; 13(1):29; doi: 10.1038/s41419-021-04478-x
306.
WangN, LuY, RothrauffBB, et al.Mechanotransduction pathways in articular chondrocytes and the emerging role of estrogen receptor-α. Bone Res, 2023a;11(1):13; doi: 10.1038/s41413-023-00248-x
307.
WangP, YangC, LuJ, et al.Sirt1 protects against intervertebral disc degeneration induced by 1,25-dihydroxyvitamin D insufficiency in mice by inhibiting the NF-κB inflammatory pathway. J Orthop Translat, 2023b;40:13–26; doi: 10.1016/j.jot.2023.04.003
308.
WangSZ, RuiYF, LuJ, et al.Cell and molecular biology of intervertebral disc degeneration: Current understanding and implications for potential therapeutic strategies. Cell Prolif, 2014; 47(5):381–390; doi: 10.1111/cpr.12121
309.
WangW, ZhangLM, GuoC, et al.Resveratrol promotes osteoblastic differentiation in a rat model of postmenopausal osteoporosis by regulating autophagy. Nutr Metab (Lond), 2020b;17:29; doi: 10.1186/s12986-020-00449-9
310.
WangX, LiZ, LiuC, et al.Multi-target renal protection in AKI: Exercise-mediated coordination of AMPK energy homeostasis, mTOR autophagy regulation, and NF-κB inflammatory control. Free Radic Biol Med, 2025b;240:397–409; doi: 10.1016/j.freeradbiomed.2025.08.030
311.
WangX, ShenT, LianJ, et al.Resveratrol reduces ROS-induced ferroptosis by activating SIRT3 and compensating the GSH/GPX4 pathway. Mol Med, 2023c;29(1):137; doi: 10.1186/s10020-023-00730-6
312.
WangX, WeiW, KrzeszinskiJY, et al.A liver-bone endocrine relay by IGFBP1 promotes osteoclastogenesis and mediates FGF21-induced bone resorption. Cell Metab, 2015; 22(5):811–824; doi: 10.1016/j.cmet.2015.09.010
313.
WangXX, WangXL, TongMM, et al.SIRT6 protects cardiomyocytes against ischemia/reperfusion injury by augmenting FoxO3α-dependent antioxidant defense mechanisms. Basic Res Cardiol, 2016a;111(2):13; doi: 10.1007/s00395-016-0531-z
314.
WangY, JinZ, JiaS, et al.Mechanical stress protects against chondrocyte pyroptosis through TGF-β1-mediated activation of Smad2/3 and inhibition of the NF-κB signaling pathway in an osteoarthritis model. Biomed Pharmacother, 2023d;159:114216; doi: 10.1016/j.biopha.2023.114216
315.
WangY, LiangB, LauWB, et al.Restoring diabetes-induced autophagic flux arrest in ischemic/reperfused heart by ADIPOR (adiponectin receptor) activation involves both AMPK-dependent and AMPK-independent signaling. Autophagy, 2017b;13(11):1855–1869; doi: 10.1080/15548627.2017.1358848
316.
WangY, ShiY, HuangY, et al.Resveratrol mediates mechanical allodynia through modulating inflammatory response via the TREM2-autophagy axis in SNI rat model. J Neuroinflammation, 2020c;17(1):311; doi: 10.1186/s12974-020-01991-2
317.
WangYT, ZhengSY, JiangSD, et al.Irisin in degenerative musculoskeletal diseases: Functions in system and potential in therapy. Pharmacol Res, 2024; 210:107480; doi: 10.1016/j.phrs.2024.107480
318.
WangZ, MaJ, MiaoZ, et al.Ergothioneine inhibits the progression of osteoarthritis via the Sirt6/NF-κB axis both in vitro and in vivo. Int Immunopharmacol, 2023e;119:110211; doi: 10.1016/j.intimp.2023.110211
319.
WangZ, TangJ, LiY, et al.AdipoRon promotes diabetic fracture repair through endochondral ossification-based bone repair by enhancing survival and differentiation of chondrocytes. Exp Cell Res, 2020d;387(2):111757; doi: 10.1016/j.yexcr.2019.111757
320.
WangZM, ChenYC, WangDP. Resveratrol, a natural antioxidant, protects monosodium iodoacetate-induced osteoarthritic pain in rats. Biomed Pharmacother, 2016b;83:763–770; doi: 10.1016/j.biopha.2016.06.050
321.
WeiL, ChaiS, YueC, et al.Resveratrol protects osteocytes against oxidative stress in ovariectomized rats through AMPK/JNK1-dependent pathway leading to promotion of autophagy and inhibition of apoptosis. Cell Death Discov, 2023; 9(1):16; doi: 10.1038/s41420-023-01331-2
322.
WeiL, PanQ, TengJ, et al.Intra-articular administration of PLGA resveratrol sustained-release nanoparticles attenuates the development of rat osteoarthritis. Mater Today Bio, 2024; 24:100884; doi: 10.1016/j.mtbio.2023.100884
323.
WeiW, PengC, GuR, et al.Urolithin A attenuates RANKL-induced osteoclastogenesis by co-regulating the p38 MAPK and Nrf2 signaling pathway. Eur J Pharmacol, 2022; 921:174865; doi: 10.1016/j.ejphar.2022.174865
324.
WeiY, JiaJ, JinX, et al.Resveratrol ameliorates inflammatory damage and protects against osteoarthritis in a rat model of osteoarthritis. Mol Med Rep, 2018; 17(1):1493–1498; doi: 10.3892/mmr.2017.8036
325.
WeidlerC, HolzerC, HarbuzM, et al.Low density of sympathetic nerve fibres and increased density of brain derived neurotrophic factor positive cells in RA synovium. Ann Rheum Dis, 2005; 64(1):13–20; doi: 10.1136/ard.2003.016154
326.
WenP, SunZ, YangD, et al.Irisin regulates oxidative stress and mitochondrial dysfunction through the UCP2-AMPK pathway in prion diseases. Cell Death Dis, 2025; 16(1):66; doi: 10.1038/s41419-025-07390-w
327.
WenW, ChenX, HuangZ, et al.Resveratrol regulates muscle fiber type conversion via miR-22-3p and AMPK/SIRT1/PGC-1α pathway. J Nutr Biochem, 2020; 77:108297; doi: 10.1016/j.jnutbio.2019.108297
328.
WernerC, HanhounM, WidmannT, et al.Effects of physical exercise on myocardial telomere-regulating proteins, survival pathways, and apoptosis. J Am Coll Cardiol, 2008; 52(6):470–482; doi: 10.1016/j.jacc.2008.04.034
329.
WiegertjesR, van CaamA, van BeuningenH, et al.TGF-β dampens IL-6 signaling in articular chondrocytes by decreasing IL-6 receptor expression. Osteoarthritis Cartilage, 2019; 27(8):1197–1207; doi: 10.1016/j.joca.2019.04.014
330.
WilsonL, PollardAE, PenfoldL, et al.Chronic activation of AMP-activated protein kinase leads to early-onset polycystic kidney phenotype. Clin Sci (Lond), 2021; 135(20):2393–2408; doi: 10.1042/cs20210821
331.
WithamMD, McDonaldC, WilsonN, et al.Metformin and physical performance in older people with probable sarcopenia and physical prefrailty or frailty in England (MET-PREVENT): A double-blind, randomised, placebo-controlled trial. Lancet Healthy Longev, 2025; 6(3):100695; doi: 10.1016/j.lanhl.2025.100695
332.
WojszelA, ŚliwowskiJ, RentflejszJ, et al.Irisin, Brain-Derived Neurotrophic Factor (BDNF), and redox balance in geriatric dynapenia. Antioxidants (Basel), 2025; 14(10):1268; doi: 10.3390/antiox14101268
333.
WoldtE, SebtiY, SoltLA, et al.Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy. Nat Med, 2013; 19(8):1039–1046; doi: 10.1038/nm.3213
334.
WongAY, SamartzisD, MaherC. The global burden of osteoarthritis: Past and future perspectives. Lancet Rheumatol, 2023; 5(9):e496–e497; doi: 10.1016/s2665-9913(23)00207-2
335.
WongRH, Thaung ZawJJ, XianCJ, et al.Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: A randomized, placebo-controlled trial. J Bone Miner Res, 2020; 35(11):2121–2131; doi: 10.1002/jbmr.4115
336.
WuCL, ChenSD, YinJH, et al.Nuclear Factor-kappaB-dependent sestrin2 induction mediates the antioxidant effects of BDNF against mitochondrial inhibition in rat cortical neurons. Mol Neurobiol, 2016; 53(6):4126–4142; doi: 10.1007/s12035-015-9357-1
337.
WuMC, NforON, HoCC, et al.The association between different impact exercises and osteoporosis: An analysis of data from the Taiwan biobank. BMC Public Health, 2024a;24(1):1881; doi: 10.1186/s12889-024-19403-y
338.
WuRE, HuangWC, LiaoCC, et al.Resveratrol protects against physical fatigue and improves exercise performance in mice. Molecules, 2013; 18(4):4689–4702; doi: 10.3390/molecules18044689
339.
WuSK, WangL, WangF, et al.Resveratrol improved mitochondrial biogenesis by activating SIRT1/PGC-1α signal pathway in SAP. Sci Rep, 2024b;14(1):26216; doi: 10.1038/s41598-024-76825-9
340.
XiaQ, ZhaoY, DongH, et al.Progress in the study of molecular mechanisms of intervertebral disc degeneration. Biomed Pharmacother, 2024; 174:116593; doi: 10.1016/j.biopha.2024.116593
341.
XiangHC, LinLX, HuXF, et al.AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1β expression. J Neuroinflammation, 2019; 16(1):34; doi: 10.1186/s12974-019-1411-x
342.
XiaoPL, CuiAY, HsuCJ, et al.Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: A systematic review and meta-analysis. Osteoporos Int, 2022; 33(10):2137–2153; doi: 10.1007/s00198-022-06454-3
343.
XieX, HuL, MiB, et al.Metformin alleviates bone loss in ovariectomized mice through inhibition of autophagy of osteoclast precursors mediated by E2F1. Cell Commun Signal, 2022; 20(1):165; doi: 10.1186/s12964-022-00966-5
344.
XuN, CuiG, ZhaoS, et al.Therapeutic effects of mechanical stress-induced C2C12-derived exosomes on glucocorticoid-induced osteoporosis through miR-92a-3p/PTEN/AKT signaling pathway. Int J Nanomedicine, 2023; 18:7583–7603; doi: 10.2147/ijn.S435301
345.
XuX, LiuX, YangY, et al.Resveratrol exerts anti-osteoarthritic effect by inhibiting TLR4/NF-κB signaling pathway via the TLR4/Akt/FoxO1 axis in IL-1β-stimulated SW1353 cells. Drug Des Devel Ther, 2020; 14:2079–2090; doi: 10.2147/dddt.S244059
346.
XueY, HuS, ChenC, et al.Myokine Irisin promotes osteogenesis by activating BMP/SMAD signaling via αV integrin and regulates bone mass in mice. Int J Biol Sci, 2022; 18(2):572–584; doi: 10.7150/ijbs.63505
347.
YanJ, DingD, FengG, et al.Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation. Exp Ther Med, 2022; 23(3):222; doi: 10.3892/etm.2022.11146
348.
YanL, LiD, XingD, et al.Comparative efficacy and safety of exercise modalities in knee osteoarthritis: Systematic review and network meta-analysis. BMJ, 2025a;391:e085242; doi: 10.1136/bmj-2025-085242
349.
YanY, AntolinN, ZhouL, et al.Macrophages excite muscle spindles with glutamate to bolster locomotion. Nature, 2025b;637(8046):698–707; doi: 10.1038/s41586-024-08272-5
350.
YanZ, ZhuS, WangH, et al.MOTS-c inhibits Osteolysis in the Mouse Calvaria by affecting osteocyte-osteoclast crosstalk and inhibiting inflammation. Pharmacol Res, 2019; 147:104381; doi: 10.1016/j.phrs.2019.104381
351.
YangC, ChenL, GuoX, et al.The vitamin D-Sirt1/PGC1α axis regulates bone metabolism and counteracts osteoporosis. J Orthop Translat, 2025; 50:211–222; doi: 10.1016/j.jot.2024.10.011
352.
YangK, WangX, ZhangC, et al.Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis. Cell Death Dis, 2024a;15(11):795; doi: 10.1038/s41419-024-07177-5
353.
YangL, LiX, JiangA, et al.Metformin alleviates lead-induced mitochondrial fragmentation via AMPK/Nrf2 activation in SH-SY5Y cells. Redox Biol, 2020; 36:101626; doi: 10.1016/j.redox.2020.101626
354.
YangR, CaoD, SuoJ, et al.Premature aging of skeletal stem/progenitor cells rather than osteoblasts causes bone loss with decreased mechanosensation. Bone Res, 2023a;11(1):35; doi: 10.1038/s41413-023-00269-6
355.
YangS, SunM, ZhangX. Protective effect of resveratrol on knee osteoarthritis and its molecular mechanisms: A recent review in preclinical and clinical trials. Front Pharmacol, 2022; 13:921003; doi: 10.3389/fphar.2022.921003
356.
YangS, YangG, WangX, et al.MicroRNA-92b in the skeletal muscle regulates exercise capacity via modulation of glucose metabolism. J Cachexia Sarcopenia Muscle, 2023b;14(6):2925–2938; doi: 10.1002/jcsm.13377
357.
YangW, YangY, WangY, et al.Metformin prevents the onset and progression of intervertebral disc degeneration: New insights and potential mechanisms (Review). Int J Mol Med, 2024b;54(2):71; doi: 10.3892/ijmm.2024.5395
358.
YangY, WangY, KongY, et al.Mechanical stress protects against osteoarthritis via regulation of the AMPK/NF-κB signaling pathway. J Cell Physiol, 2019; 234(6):9156–9167; doi: 10.1002/jcp.27592
359.
YenCH, ChangPS, ChangYH, et al.Identification of coenzyme Q10 and skeletal muscle protein biomarkers as potential factors to assist in the diagnosis of sarcopenia. Antioxidants (Basel), 2022; 11(4):725; doi: 10.3390/antiox11040725
360.
YinH, RuanZ, WanTF, et al.Metformin ameliorates osteoporosis by enhancing bone angiogenesis via the YAP1/TAZ-HIF1α axis. Mol Med, 2025; 31(1):122; doi: 10.1186/s10020-025-01169-7
361.
YuC, SunR, YangW, et al.Exercise ameliorates osteopenia in mice via intestinal microbial-mediated bile acid metabolism pathway. Theranostics, 2025; 15(5):1741–1759; doi: 10.7150/thno.104186
362.
YuD, YeX, CheR, et al.FGF21 exerts comparable pharmacological efficacy with Adalimumab in ameliorating collagen-induced rheumatoid arthritis by regulating systematic inflammatory response. Biomed Pharmacother, 2017; 89:751–760; doi: 10.1016/j.biopha.2017.02.059
363.
YuY, HeJ, LiS, et al.Fibroblast growth factor 21 (FGF21) inhibits macrophage-mediated inflammation by activating Nrf2 and suppressing the NF-κB signaling pathway. Int Immunopharmacol, 2016; 38:144–152; doi: 10.1016/j.intimp.2016.05.026
364.
YuanW, LiZX, ZhaoCL, et al.Attenuation of the degenerative effects of endothelin-1 on cartilaginous end plate cells by the endothelin receptor antagonist BQ-123 via the Wnt/β-catenin signaling pathway. Spine J, 2018; 18(9):1669–1677; doi: 10.1016/j.spinee.2018.05.012
365.
ZhangDM, CuiDX, XuRS, et al.Phenotypic research on senile osteoporosis caused by SIRT6 deficiency. Int J Oral Sci, 2016; 8(2):84–92; doi: 10.1038/ijos.2015.57
366.
ZhangJ, LiJ, LiuY, et al.Effect of resveratrol on skeletal slow-twitch muscle fiber expression via AMPK/PGC-1α signaling pathway in bovine myotubes. Meat Sci, 2023; 204:109287; doi: 10.1016/j.meatsci.2023.109287
367.
ZhangL, YuanY, WuW, et al.Medium-intensity treadmill exercise exerts beneficial effects on bone modeling through bone marrow mesenchymal stromal cells. Front Cell Dev Biol, 2020a;8:600639; doi: 10.3389/fcell.2020.600639
368.
ZhangL, ZhengYL, WangR, et al.Exercise for osteoporosis: A literature review of pathology and mechanism. Front Immunol, 2022a;13:1005665; doi: 10.3389/fimmu.2022.1005665
369.
ZhangL, ZhuY, ChengH, et al.The increased expression of estrogen-related receptor α correlates with Wnt5a and poor prognosis in patients with glioma. Mol Cancer Ther, 2019; 18(1):173–184; doi: 10.1158/1535-7163.Mct-17-0782
370.
ZhangR, MuX, LiuD, et al.Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency. J Nanobiotechnology, 2024; 22(1):580; doi: 10.1186/s12951-024-02829-2
371.
ZhangS, WuX, WangJ, et al.Adiponectin/AdiopR1 signaling prevents mitochondrial dysfunction and oxidative injury after traumatic brain injury in a SIRT3 dependent manner. Redox Biol, 2022b;54:102390; doi: 10.1016/j.redox.2022.102390
372.
ZhangW, NukiG, MoskowitzRW, et al.OARSI recommendations for the management of hip and knee osteoarthritis: Part III: Changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage, 2010; 18(4):476–499; doi: 10.1016/j.joca.2010.01.013
373.
ZhangX, HuC, KongCY, et al.FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT. Cell Death Differ, 2020b;27(2):540–555; doi: 10.1038/s41418-019-0372-z
374.
ZhangX, LiuX, WanF, et al.Protective effect of resveratrol against hydrogen peroxide-induced oxidative stress in bovine skeletal muscle cells. Meat Sci, 2022c;185:108724; doi: 10.1016/j.meatsci.2021.108724
375.
ZhangX, ZhangP, ZhuY, et al.Myogenic nano-adjuvant for orthopedic-related sarcopenia via mitochondrial homeostasis modulation in macrophage-myosatellite metabolic crosstalk. J Nanobiotechnology, 2025a;23(1):390; doi: 10.1186/s12951-025-03480-1
376.
ZhangY, HeX, WangK, et al.Irisin alleviates obesity-induced bone loss by inhibiting interleukin 6 expression via TLR4/MyD88/NF-κB axis in adipocytes. J Adv Res, 2025b;69:343–359; doi: 10.1016/j.jare.2024.04.013
377.
ZhangY, LiS, JinP, et al.Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis. Nat Commun, 2022d;13(1):2447; doi: 10.1038/s41467-022-30119-8
378.
ZhangZ, SongY, WangSI, et al.Osteoblasts/osteocytes sirtuin6 is vital to preventing ischemic osteonecrosis through targeting VDR-RANKL signaling. J Bone Miner Res, 2021; 36(3):579–590; doi: 10.1002/jbmr.4207
379.
ZhaoK, CuiY, DuY, et al.Exercise mimetic exosomes re-establish the extracellular matrix metabolic balance and alleviate the inflammatory macrophage infiltration in intervertebral disc degeneration. Adv Healthc Mater, 2025; 14(20):e2500219; doi: 10.1002/adhm.202500219
380.
ZhaoY, DongD, ReeceEA, et al.Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy. Am J Obstet Gynecol, 2018; 218(1):136.e131–136.e110; doi: 10.1016/j.ajog.2017.10.040
381.
ZhengL, ShenX, XieY, et al.Metformin promotes osteogenic differentiation and prevents hyperglycaemia-induced osteoporosis by suppressing PPARγ expression. Acta Biochim Biophys Sin (Shanghai), 2023; 55(3):394–403; doi: 10.3724/abbs.2023043
382.
ZhengZY, YangPL, LiRY, et al.STAT3β disrupted mitochondrial electron transport chain enhances chemosensitivity by inducing pyroptosis in esophageal squamous cell carcinoma. Cancer Lett, 2021; 522:171–183; doi: 10.1016/j.canlet.2021.09.035
383.
ZhouB, PengK, WangG, et al.miR-483-3p promotes the osteogenesis of human osteoblasts by targeting Dikkopf 2 (DKK2) and the Wnt signaling pathway. Int J Mol Med, 2020; 46(4):1571–1581; doi: 10.3892/ijmm.2020.4694
384.
ZhouK, QiaoX, CaiY, et al.Lower circulating irisin in middle-aged and older adults with osteoporosis: a systematic review and meta-analysis. Menopause, 2019a;26(11):1302–1310; doi: 10.1097/gme.0000000000001388
385.
ZhouL, SongHY, GaoLL, et al.MicroRNA-100-5p inhibits osteoclastogenesis and bone resorption by regulating fibroblast growth factor 21. Int J Mol Med, 2019b;43(2):727–738; doi: 10.3892/ijmm.2018.4017
386.
ZhouT, YanY, ZhaoC, et al.Resveratrol improves osteogenic differentiation of senescent bone mesenchymal stem cells through inhibiting endogenous reactive oxygen species production via AMPK activation. Redox Rep, 2019c;24(1):62–69; doi: 10.1080/13510002.2019.1658376
387.
ZhouW, ShiY, WangH, et al.Exercise-induced FNDC5/irisin protects nucleus pulposus cells against senescence and apoptosis by activating autophagy. Exp Mol Med, 2022a;54(7):1038–1048; doi: 10.1038/s12276-022-00811-2
388.
ZhouXH, LuoYX, YaoXQ. Exercise-driven cellular autophagy: A bridge to systematic wellness. J Adv Res, 2025; 76:271–291; doi: 10.1016/j.jare.2024.12.036
389.
ZhouY, FanX, JiaoT, et al.SIRT6 as a key event linking P53 and NRF2 counteracts APAP-induced hepatotoxicity through inhibiting oxidative stress and promoting hepatocyte proliferation. Acta Pharm Sin B, 2021a;11(1):89–99; doi: 10.1016/j.apsb.2020.06.016
390.
ZhouY, LiM, WangZ, et al.AMPK/Drp1 pathway mediates Streptococcus uberis-Induced mitochondrial dysfunction. Int Immunopharmacol, 2022b;113(Pt A):109413; doi: 10.1016/j.intimp.2022.109413
391.
ZhouY, MingJ, LiY, et al.Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis. Cell Death Discov, 2021b;7(1):37; doi: 10.1038/s41420-021-00418-y
392.
ZhouZM, BaoJP, PengX, et al.Small extracellular vesicles from hypoxic mesenchymal stem cells alleviate intervertebral disc degeneration by delivering miR-17-5p. Acta Biomater, 2022c;140:641–658; doi: 10.1016/j.actbio.2021.11.044
393.
ZhuD, ZhangX, WangF, et al.Irisin rescues diabetic cardiac microvascular injury via ERK1/2/Nrf2/HO-1 mediated inhibition of oxidative stress. Diabetes Res Clin Pract, 2022a;183:109170; doi: 10.1016/j.diabres.2021.109170
394.
ZhuJ, YangS, QiY, et al.Stem cell-homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model. Sci Adv, 2022b;8(13):eabk0011; doi: 10.1126/sciadv.abk0011
395.
ZhuWG, ThomasACQ, WilsonGM, et al.Identification of a resistance-exercise-specific signalling pathway that drives skeletal muscle growth. Nat Metab, 2025; 7(7):1404–1423; doi: 10.1038/s42255-025-01298-7
396.
ZimmermannHR, YangW, KasicaNP, et al.Brain-specific repression of AMPKα1 alleviates pathophysiology in Alzheimer’s model mice. J Clin Invest, 2020; 130(7):3511–3527; doi: 10.1172/jci133982
397.
ZouZ, HuW, KangF, et al.Interplay between lipid dysregulation and ferroptosis in chondrocytes and the targeted therapy effect of metformin on osteoarthritis. J Adv Res, 2025; 69:515–529; doi: 10.1016/j.jare.2024.04.012
