Massive rotator cuff tears (RCTs) begin as primary tendon injuries and cause a myriad of changes in the muscle, including atrophy, fatty infiltration (FI), and fibrosis. However, it is unclear which changes are most closely associated with muscle function.
Purpose:
To determine if FI of the supraspinatus muscle after acute RCT relates to short-term changes in muscle function.
Study Design:
Controlled laboratory study.
Methods:
Unilateral RCTs were induced in female rabbits via tenotomy of the supraspinatus and infraspinatus. Maximal isometric force and rate of fatigue were measured in the supraspinatus in vivo at 6 and 12 weeks after tenotomy. Computed tomography scanning was performed, followed by histologic analysis of myofiber size, FI, and fibrosis.
Results:
Tenotomy resulted in supraspinatus weakness, reduced myofiber size, FI, and fibrosis, but no differences were evident between 6 and 12 weeks after tenotomy except for increased collagen content at 12 weeks. FI was a predictor of supraspinatus weakness and was strongly correlated to force, even after accounting for muscle cross-sectional area. While muscle atrophy accounted for the loss in force in tenotomized muscles with minimal FI, it did not account for the greater loss in force in tenotomized muscles with the most FI. Collagen content was not strongly correlated with maximal isometric force, even when normalized to muscle size.
Conclusion:
After RCT, muscle atrophy results in the loss of contractile force from the supraspinatus, but exacerbated weakness is observed with increased FI. Therefore, the level of FI can help predict contractile function of torn rotator cuff muscles.
Clinical Relevance:
Markers to predict contractile function of RCTs will help determine the appropriate treatment to improve functional recovery after RCTs.
BaumannCWKwakDLiuHMThompsonLV. Age-induced oxidative stress: how does it influence skeletal muscle quantity and quality?J Appl Physiol (1985). 2016;121(5):1047-1052.
2.
BayerMLYeungCYKadlerKEet al. The initiation of embryonic-like collagen fibrillogenesis by adult human tendon fibroblasts when cultured under tension. Biomaterials. 2010;31(18):4889-4897.
3.
BirbrairAZhangTWangZMet al. Role of pericytes in skeletal muscle regeneration and fat accumulation. Stem Cells Dev. 2013;22(16):2298-2314.
4.
BriguetACourdier-FruhIFosterMMeierTMagyarJP. Histological parameters for the quantitative assessment of muscular dystrophy in the mdx-mouse. Neuromuscul Disord. 2004;14(10):675-682.
5.
BryanBAMitchellDCZhaoLet al. Modulation of muscle regeneration, myogenesis, and adipogenesis by the rho family guanine nucleotide exchange factor GEFT. Mol Cell Biol. 2005;25(24):11089-11101.
6.
BuckMChojkierM. Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J. 1996;15(8):1753-1765.
7.
ChoiSHChungKYJohnsonBJet al. Co-culture of bovine muscle satellite cells with preadipocytes increases PPARgamma and C/EBPbeta gene expression in differentiated myoblasts and increases GPR43 gene expression in adipocytes. J Nutr Biochem. 2013;24(3):539-543.
8.
DaviesMRLiuXLeeLet al. TGF-beta small molecule inhibitor SB431542 reduces rotator cuff muscle fibrosis and fatty infiltration by promoting fibro/adipogenic progenitor apoptosis. PLoS One. 2016;11(5):e0155486.
9.
DavisMEKornMAGumucioJPet al. Simvastatin reduces fibrosis and protects against muscle weakness after massive rotator cuff tear. J Shoulder Elbow Surg. 2015;24(2):280-287.
10.
DavisMEStaffordPLJergensonMJBediAMendiasCL. Muscle fibers are injured at the time of acute and chronic rotator cuff repair. Clin Orthop Relat Res. 2015;473(1):226-232.
11.
DellavalleAMaroliGCovarelloDet al. Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells. Nat Commun. 2011;2:499.
12.
DenizGKoseOTugayAGulerFTuranA. Fatty degeneration and atrophy of the rotator cuff muscles after arthroscopic repair: does it improve, halt or deteriorate?Arch Orthop Trauma Surg. 2014;134(7):985-990.
13.
DitsiosKBoutsiadisAKapoukranidouDet al. Chronic massive rotator cuff tear in rats: in vivo evaluation of muscle force and three-dimensional histologic analysis. J Shoulder Elbow Surg. 2014;23(12):1822-1830.
14.
DunnWRSchackmanBRWalshCet al. Variation in orthopaedic surgeons’ perceptions about the indications for rotator cuff surgery. J Bone Joint Surg Am. 2005;87(9):1978-1984.
15.
FabisJDanilewiczMZwierzchowskiJTNiedzielskiK. Atrophy of type I and II muscle fibers is reversible in the case of grade >2 fatty degeneration of the supraspinatus muscle: an experimental study in rabbits. J Shoulder Elbow Surg. 2016;25(3):487-492.
16.
FabisJKordekPBoguckiAMazanowska-GajdowiczJ. Function of the rabbit supraspinatus muscle after large detachment of its tendon: 6-week, 3-month, and 6-month observation. J Shoulder Elbow Surg. 2000;9(3):211-216.
17.
GerberCFuchsBHodlerJ. The results of repair of massive tears of the rotator cuff. J Bone Joint Surg Am. 2000;82(4):505-515.
18.
GerberCMeyerDCFluckMBennMCvon RechenbergBWieserK. Anabolic steroids reduce muscle degeneration associated with rotator cuff tendon release in sheep. Am J Sports Med. 2015;43(10):2393-2400.
19.
GerberCSchneebergerAGHoppelerHMeyerDC. Correlation of atrophy and fatty infiltration on strength and integrity of rotator cuff repairs: a study in thirteen patients. J Shoulder Elbow Surg. 2007;16(6):691-696.
20.
GibbonsMCSinghAAnakwenzeOet al. Histological evidence of muscle degeneration in advanced human rotator cuff disease. J Bone Joint Surg Am. 2017;99(3):190-199.
21.
GilliesARLieberRL. Structure and function of the skeletal muscle extracellular matrix. Muscle Nerve. 2011;44(3):318-331.
22.
GimbelJAVan KleunenJPLakeSPWilliamsGRSoslowskyLJ. The role of repair tension on tendon to bone healing in an animal model of chronic rotator cuff tears. J Biomech. 2007;40(3):561-568.
23.
GladstoneJNBishopJYLoIKFlatowEL. Fatty infiltration and atrophy of the rotator cuff do not improve after rotator cuff repair and correlate with poor functional outcome. Am J Sports Med. 2007;35(5):719-728.
24.
GumucioJPDavisMEBradleyJRet al. Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy. J Orthop Res. 2012;30(12):1963-1970.
25.
GumucioJPFloodMDBediAKramerHFRussellAJMendiasCL. Inhibition of prolyl 4-hydroxylase decreases muscle fibrosis following chronic rotator cuff tear. Bone Joint Res. 2017;6(1):57-65.
26.
GumucioJPFloodMDRocheSMet al. Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear. Int Orthop. 2016;40(4):759-764.
27.
HamanoNYamamotoAShitaraHet al. Does successful rotator cuff repair improve muscle atrophy and fatty infiltration of the rotator cuff? A retrospective magnetic resonance imaging study performed shortly after surgery as a reference. J Shoulder Elbow Surg. 2017;26(6):967-974.
28.
HosoyamaTIshiguroNYamanouchiKNishiharaM. Degenerative muscle fiber accelerates adipogenesis of intramuscular cells via RhoA signaling pathway. Differentiation. 2009;77(4):350-359.
29.
HsuHCBoardmanND3rdLuoZPAnKN. Tendon-defect and muscle-unloaded models for relating a rotator cuff tear to glenohumeral stability. J Orthop Res. 2000;18(6):952-958.
30.
HuangAHLuHHSchweitzerR. Molecular regulation of tendon cell fate during development. J Orthop Res. 2015;33(6):800-812.
31.
JamaliAAAfsharPAbramsRALieberRL. Skeletal muscle response to tenotomy. Muscle Nerve. 2000;23(6):851-862.
32.
JoCHKimJEYoonKSet al. Does platelet-rich plasma accelerate recovery after rotator cuff repair? A prospective cohort study. Am J Sports Med. 2011;39(10):2082-2090.
33.
KronbergMNemethGBrostromLA. Muscle activity and coordination in the normal shoulder: an electromyographic study. Clin Orthop Relat Res. 1990;257:76-85.
34.
Lamounier-ZepterVEhrhart-BornsteinMKarczewskiPHaaseHBornsteinSRMoranoI. Human adipocytes attenuate cardiomyocyte contraction: characterization of an adipocyte-derived negative inotropic activity. FASEB J. 2006;20(10):1653-1659.
35.
LaurensCLoucheKSengenesCet al. Adipogenic progenitors from obese human skeletal muscle give rise to functional white adipocytes that contribute to insulin resistance. Int J Obes (Lond). 2016;40(3):497-506.
36.
LieberRLWardSR. Cellular mechanisms of tissue fibrosis: 4. Structural and functional consequences of skeletal muscle fibrosis. Am J Physiol Cell Physiol. 2013;305(3):C241-C252.
37.
LiuXManzanoGKimHTFeeleyBT. A rat model of massive rotator cuff tears. J Orthop Res. 2011;29(4):588-595.
38.
LiuXNingAYChangNCet al. Investigating the cellular origin of rotator cuff muscle fatty infiltration and fibrosis after injury. Muscles Ligaments Tendons J. 2016;6(1):6-15.
39.
MeyerDCGerberCVon RechenbergBWirthSHFarshadM. Amplitude and strength of muscle contraction are reduced in experimental tears of the rotator cuff. Am J Sports Med. 2011;39(7):1456-1461.
40.
MoragYJacobsonJAMillerBDe MaeseneerMGirishGJamadarD. MR imaging of rotator cuff injury: what the clinician needs to know. Radiographics. 2006;26(4):1045-1065.
41.
OhMNorJE. The perivascular niche and self-renewal of stem cells. Front Physiol. 2015;6:367.
42.
PatelTJLieberRL. Force transmission in skeletal muscle: from actomyosin to external tendons. Exerc Sport Sci Rev. 1997;25:321-363.
43.
PellegrinelliVRouaultCRodriguez-CuencaSet al. Human adipocytes induce inflammation and atrophy in muscle cells during obesity. Diabetes. 2015;64(9):3121-3134.
44.
RandelliPMenonARagoneVet al. Effects of the pulsed electromagnetic field PST(R) on human tendon stem cells: a controlled laboratory study. BMC Complement Altern Med. 2016;16:293.
45.
RowshanKHadleySPhamKCaiozzoVLeeTQGuptaR. Development of fatty atrophy after neurologic and rotator cuff injuries in an animal model of rotator cuff pathology. J Bone Joint Surg Am. 2010;92(13):2270-2278.
46.
RubinoLJStillsHFJrSprottDCCrosbyLA. Fatty infiltration of the torn rotator cuff worsens over time in a rabbit model. Arthroscopy. 2007;23(7):717-722.
47.
SatoEJKillianMLChoiAJet al. Skeletal muscle fibrosis and stiffness increase after rotator cuff tendon injury and neuromuscular compromise in a rat model. J Orthop Res. 2014;32(9):1111-1116.
48.
SchmutzSFuchsTRegenfelderFSteinmannPZumsteinMFuchsB. Expression of atrophy mRNA relates to tendon tear size in supraspinatus muscle. Clin Orthop Relat Res. 2009;467(2):457-464.
49.
ShirasawaHMatsumuraNShimodaMet al. Inhibition of PDGFR signaling prevents muscular fatty infiltration after rotator cuff tear in mice. Sci Rep. 2017;7:41552.
50.
SteinbacherPTauberMKoglerSStoiberWReschHSangerAM. Effects of rotator cuff ruptures on the cellular and intracellular composition of the human supraspinatus muscle. Tissue Cell. 2010;42(1):37-41.
51.
SuWRBudoffJELuoZP. Posterosuperior displacement due to rotator cuff tears. Arthroscopy. 2011;27(11):1472-1477.
52.
TakagishiKSaitohATonegawaMIkedaTItomanM. Isolated paralysis of the infraspinatus muscle. J Bone Joint Surg Br. 1994;76(4):584-587.
53.
TakegaharaYYamanouchiKNakamuraKNakanoSNishiharaM. Myotube formation is affected by adipogenic lineage cells in a cell-to-cell contact-independent manner. Exp Cell Res. 2014;324(1):105-114.
54.
TrudelGRyanSERakhraKUhthoffHK. Extra- and intramuscular fat accumulation early after rabbit supraspinatus tendon division: depiction with CT. Radiology. 2010;255(2):434-441.
55.
UhthoffHKColettaETrudelG. Intramuscular fat accumulation and muscle atrophy in the absence of muscle retraction. Bone Joint Res. 2014;3(4):117-122.
56.
UhthoffHKMatsumotoFTrudelGHimoriK. Early reattachment does not reverse atrophy and fat accumulation of the supraspinatus—an experimental study in rabbits. J Orthop Res. 2003;21(3):386-392.
57.
ValenciaAPIyerSRPrattSJGilotraMNLoveringRM. A method to test contractility of the supraspinatus muscle in mouse, rat, and rabbit. J Appl Physiol (1985). 2016;120(3):310-317.
58.
WarthRJDornanGJJamesEWHoranMPMillettPJ. Clinical and structural outcomes after arthroscopic repair of full-thickness rotator cuff tears with and without platelet-rich product supplementation: a meta-analysis and meta-regression. Arthroscopy. 2015;31(2):306-320.
ZhengBCaoBCrisanMet al. Prospective identification of myogenic endothelial cells in human skeletal muscle. Nat Biotechnol. 2007;25(9):1025-1034.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
