Gastrectomy (Gx) leads to osteopenia/osteoporosis in humans and animals. However, little is known about the influence of Gx on the cartilage in this regard. Recent studies have demonstrated a protective effect of 2-oxoglutaric acid (2-Ox) on bone and cartilage. Hence, the purpose of this study was to investigate whether 2-Ox can mitigate eventual Gx-induced cartilage impairment. Twenty female Sprague-Dawley rats were subjected to Gx and randomly divided into two groups: Gx + 2-Ox and Gx. Another 20 rats were sham-operated (ShO) and randomly divided into two groups: ShO + 2-Ox and ShO. The daily dose of 2-Ox administered to the rats in the drinking water was 0.43 g per 100 g rat. After eight weeks, rats were euthanized and femora and tibiae were collected. Histology and histomorphometry analyses of the articular cartilage and the growth plate were done. Gx resulted in a 32% (±44.5 femur, ±35.8 tibia) decrease in overall thickness of articular cartilage in both bones (femur: ShO 279.1 ± 48.5 vs. Gx 190.2 ± 38.4 µm, tibia: ShO 222.9 ± 50.3 µm vs. Gx 151.3 ± 52.6 µm) (in some zones up to 58 ± 28.0%), and in the growth plate up to 20% (±22.4) (femur: ShO 243.0 ± 34.0 vs. Gx 207.0 ± 33.7 µm, tibia: ShO 220.0 ± 24.6 µm vs. Gx 171.1 ± 16.1 µm). Gx altered the spatial distribution of thick and thin collagen fibers, and chondrocyte shape and size. 2-Ox administration prevented the reduction in both cartilages thickness (Gx + 2-Ox: articular cartilage 265.2 ± 53.8 µm, 235.6 ± 42.7 µm, growth plate 236.7 ± 39.2 µm, 191.3 ± 16.5 µm in femur and tibia, respectively), and abolished the spatial changes in collagen distribution and structure induced by Gx. Gx affects cartilage structure and thickness, however, 2-Ox administration mitigates these effects and showed protective and stimulatory properties. Our observations suggest that dietary 2-Ox can be used to offset some of the changes in hyaline cartilage, in particular articular cartilage, following bariatric surgeries.
AlqahtaniARAntonisamyBAlamriHElahmediMZimmermanVA. Laparoscopic sleeve gastrectomy in 108 obese children and adolescents aged 5 to 21 years. Ann Surg2012; 256: 266–73.
2.
SangheraTSKangSNHamdanK. Metabolic bone disease and bariatric surgery. Rheumatol Curr Res2012; S5: 001–001.
3.
Williams SE. Metabolic bone disease in the bariatric surgery patient. J Obes. Epub ahead of print 2011. DOI:10.1155/2011/634614.
4.
BaekKHJeonHMLeeSSLimDJOhKWLeeWYRheeEJHanJHChaBYLeeKWSonHYKangSKKangMI. Short-term changes in bone and mineral metabolism following gastrectomy in gastric cancer patients. Bone2008; 42: 61–7.
5.
RümenapfGSchwillePOErbenRGSchreiberMFriesWSchmiedlAHohenbergerW. Osteopenia following total gastrectomy in the rat – state of mineral metabolism and bone histomorphometry. Eur Surg Res1997; 29: 209–21.
6.
Lehto-AxteliusDSurveVJohnellOHåkansonR. Effect of calcium deficiency and calcium supplementation on gastrectomy-induced osteopenia in the young male rat. Scand J Gastroenterol2002; 37: 299–306.
7.
DobrowolskiPPiersiakTSurveVVKruszewskaDGawronAPacuskaPHåkansonRPierzynowskiSG. Dietary α-ketoglutarate reduces gastrectomy-evoked loss of calvaria and trabecular bone in female rats. Scand J Gastroenterol2008; 43: 551–8.
8.
ZittelTZeebBMaierGKaiserGWZwirnerMLiebichHStarlingerMBeckerHD. High prevalence of bone disorders after gastrectomy. Am J Surg1997; 174: 431–8.
9.
LimJSKimSBBangHYCheonGJLeeJI. High prevalence of osteoporosis in patients with gastric adenocarcinoma following gastrectomy. World J Gastroenterol2007; 13: 6492–7.
10.
LimJSLeeJI. Prevalence, pathophysiology, screening and management of osteoporosis in gastric cancer patients. J Gastric Cancer2011; 11: 7–15.
11.
PerssonPGagnemo-PerssonRChenDAxelsonJNylanderAGJohnellOHåkansonR. Gastrectomy causes bone loss in the rat: Is lack of gastric acid responsible?Scand J Gastroenterol1993; 28: 301–6.
12.
Lehto-AxteliusDChenDSurveVHåkansonR. Post-gastrectomy osteopenia in the rat. Bone structure is preserved by retaining 10%–30% of the oxyntic gland area. Scand J Gastroenterol2002; 37: 437–43.
13.
ViégasMVasconcelosRSNevesAPDinizETBandeiraF. Bariatric surgery and bone metabolism a systematic review. Arq Bras Endocrinol Metab2010; 54: 158–63.
14.
RümenapfGSchwillePOErbenRGSchreiberMBergéBFriesWSchmiedlAKoromaSHohenbergerW. Gastric fundectomy in the rat: effects on mineral and bone metabolism, with emphasis on the gastrin-calcitonin-parathyroid hormone-vitamin D axis. Calcif Tissue Int1998; 63: 433–41.
15.
ZittelTMaierGStarlingerMBeckerHD. Calcium and bone metabolism after gastrectomy. Chirurg1997; 68: 784–8.
16.
InuiAIwakuraTReddiAH. Human stem cells and articular cartilage regeneration. Cells2012; 1: 994–1009.
17.
HengBCCaoTLeeEH. Directing stem cell differentiation into the chondrogenic lineage in vitro. Steam Cells2004; 22: 1152–67.
WeiYZengWWanRWangJZhouQQiuSSinghSR. Chondrogenic differentiation of induced pluripotent stem cells from osteoarthritic chondrocytes in alginate matrix. Eur Cell Mater2012; 23: 1–12.
20.
LobsteinTBaurLUauyR. Obesity in children and young people: a crisis in public health. Obes Rev2004; 5: 4–85.
21.
RadzkiRPBienkoMPierzynowskiSG. Anti-osteopenic effect of alpha-ketoglutarate sodium salt on ovariectomized rats. J Bone Miner Metab2012; 30: 651–9.
22.
HarrisonAPPierzynowskiSG. Biological effects of 2-oxoglutarate with particular emphasis on the regulation of protein, mineral and lipid absorption/metabolism, muscle performance, kidney function, bone formation and cancerogenesis, all viewed from a healthy ageing perspective state of the art – review article. J Physiol Pharmacol2008; 59: 91–106.
KristensenNBJungvidHFernandesJAPierzynowskiSG. Absorption and metabolism of α-ketoglutarate in growing pigs. J Anim Physiol Anim Nutr2002; 86: 239–45.
25.
DobrowolskiPTomaszewskaEBienkoMRadzkiRPPierzynowskiSG. The effect of dietary administration of 2-oxoglutaric acid on the cartilage and bone of growing rats. Br J Nutr2013; 110: 651–8.
26.
Suvara SK, Layton C, Bancroft JD. Bancroft's Theory and practice of histological techniques. 7th ed. Churchill Livingstone Elsevier, London, 2012.
27.
RichLWhittakerP. Collagen and picrosirius red staining: a polarized light assessment of fibrillar hue and spatial distribution. Braz J Morphol Sci2005; 22: 97–104.
28.
RoachHIMehtaGOreffoROCClarkeNMCooperC. Temporal analysis of rat growth plates cessation of growth with age despite presence of a physis. J Histochem Cytochem2003; 51: 373–83.
29.
TomaszewskaEDobrowolskiPPuzioI. Morphological changes of the cartilage and bone in newborn piglets evoked by experimentally induced glucocorticoid excess during pregnancy. J Anim Physiol Anim Nutr2013; 98: 785–96.
30.
HunzikerEBQuinnTMHauselmannHJ. Quantitative structural organization of normal adult human articular cartilage. Osteoarthritis Cartilage2002; 10: 564–72.
31.
ClaassenHSchichtMPaulsenF. Impact of sex hormones, insulin, growth factors and peptides on cartilage health and disease. Prog Histochem Cytochem2011; 45: 239–93.
32.
BobinacDSpanjolJZoricicSMaricI. Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans. Bone2003; 32: 284–90.
33.
HagiwaraYHattoriKAokiTOhgushiHItoH. Autofluorescence assessment of extracellular matrices of a cartilage-like tissue construct using a fluorescent image analyser. J Tissue Eng Regen Med2011; 5: 163–8.
34.
SokalRRRohlfFJ. Biometry, 3rd ed. New York, NY: W.H. Freeman, 1995, pp. 272–308.
35.
Lehto-AxteliusDStenströmMJohnellO. Osteopenia after gastrectomy, fundectomy or antrectomy: an experimental study in the rat. Regul Pept1998; 78: 41–50.
36.
SurveVAnderssonNAlataloSLehto-AxteliusDHalleenJVäänänenKHåkansonR. Does combined gastrectomy and ovariectomy induce greater osteopenia in young female rats than gastrectomy alone?Calcif Tissue Int2001; 69: 274–80.
37.
BuckwalterJAMankinHJGrodzinskyAJ. Articular cartilage and osteoarthritis. Instr Course Lect2005; 54: 465–80.
38.
FilipRSPierzynowskiSGLindegardBWernermanJHaratym-MajAPodgurniakM. Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: six-month study. Int J Vitam Nutr Res2007; 77: 89–97.
39.
DobrowolskiPTomaszewskaERadzkiRPBienkoMWydrychJZdybelAPierzynowskiSG. Can 2-oxoglutarate prevent changes in bone evoked by omeprazole?Nutrition2013; 29: 556–61.
40.
ŚliwaEAdaszekŁTataraMDobrowolskiP. Short- and long-term consequences on biochemical markers after fundectomy in pigs supplemented with 3-hydroxy-3-methylbutyrate and alpha-ketoglutarate. Berl Munch Tierarztl Wochenschr2010; 123: 397–405.
41.
TomaszewskaEDobrowolskiPWydrychJ. Postnatal administration of 2-oxoglutaric acid improves articular and growth plate cartilages and bone tissue morphology in pigs prenatally treated with dexamethasone. J Physiol Pharmacol2012; 63: 547–54.
AnderssonNSurveVVLehto-AxteliusDOhlssonCHåkansonRAnderssonKRybergB. Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopenia in the young female rat. J Endocrinol2002; 175: 695–703.
44.
GuilakFJonesWRTing-BeallHPLeeGM. The deformation behavior and mechanical properties of chondrocytes in articular cartilage. Osteoarthritis Cartilage1999; 7: 59–70.
45.
SugermanHJSugermanELDeMariaEJKellumJMKennedyCMoweryYWolfeLG. Bariatric surgery for severely obese adolescents. J Gastrointest Surg2003; 7: 102–7.
46.
VincentHKHeywoodKConnellyJHurleyRW. Obesity and weight loss in the treatment and prevention of osteoarthritis. PMR2012; 4: 59–67.
47.
EcksteinFMuller-GerblMPutzR. Distribution of subchondral bone density and cartilage thickness in the human patella. J Anat1992; 180: 425–33.
48.
KoszycaBFazzalariNLVernon-RobertsB. Quantitative analysis of the bone cartilage interface within the knee. Knee1996; 3: 23–31.
