Main Article Content
BACKGROUND: Muscle injuries are a common manifestation of exercise and non-mechanical factors such as drugs, genetic defects, and systemic diseases. Despite their clinical importance, the cellular and molecular mechanisms of muscle injury and repair are poorly understood, which hamper development of effective clinical interventions.
OBJECTIVE: This review is an attempt to recognize basic principles of skeletal muscle regeneration process.
METHODS: A thorough systematic review of articles on muscle injury and repair processes was conducted using three reliable search engines for biomedical literature as ScienceDirect, Scopus and PubMed.
REVIEW: Following injury, rapid activation and differentiation of satellite cells is major cellular repair process. At the molecular levels, activation of dysferlin and MG53 proteins help in building the ‘’repair cap’’ at injury site to initiate repair process. This event is followed by secretion of muscle myokines and subsequent infiltration of macrophages into muscle fibers, which remove cellular debris and activate other repair proteins and satellite cells. This review elaborates cellular and molecular mechanisms regulating these events following muscle injury. Effective therapeutic interventions to counter muscle injury-related atrophy remain elusive.
Conclusion: Altogether, this review proposes cellular and molecular targets to accelerate muscle regeneration process following mechanical and non-mechanical injuries. Further investigations are required to elucidate the pathways dictating muscle regeneration process following injury.
Work published in KMUJ is licensed under a
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
2. Yin H, Price F, Rudnicki MA. Satellite cells and the muscle stem cell niche. Physiol Rev 2013;93(1):23-67. https://doi.org/10.1152/physrev.00043.2011.
3. Mahdy MAA. Skeletal muscle fibrosis: an overview. Cell Tissue Res 2019;375(3):575-88. https://doi.org/10.1007/s00441-018-2955-2.
4. Bertini E, D'Amico A, Gualandi F, Petrini S. Congenital muscular dystrophies: a brief review. Semin Pediatr Neurol 2011;18(4):277-88. https://doi.org/10.1016/j.spen.2011.10.010.
5. Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. J Paediatr Child Health 2015;51(8):759-64. https://doi.org/10.1111/jpc.12868.
6. Qaisar R, Bhaskaran S, Premkumar P, Ranjit R, Natarajan KS, Ahn B, et al. Oxidative stress-induced dysregulation of excitation-contraction coupling contributes to muscle weakness. J Cachexia Sarcopenia Muscle 2018;9(5):1003-17. https://doi.org/10.1002/jcsm.12339.
7. Baoge L, Van Den Steen E, Rimbaut S, Philips N, Witvrouw E, Almqvist KF, et al. Treatment of skeletal muscle injury: a review. ISRN Orthop 2012;2012:689012. https://doi.org/10.5402/2012/689012.
8. Hody S, Croisier JL, Bury T, Rogister B, Leprince P. Eccentric Muscle Contractions: Risks and Benefits. Front Physiol 2019;10:536. https://doi.org/10.3389/fphys.2019.00536.
9. Qaisar R, Bhaskaran S, Van Remmen H. Muscle fiber type diversification during exercise and regeneration. Free Radic Biol Med 2016;98:56-67. https://doi.org/10.1016/j.freeradbiomed.2016.03.025.
10. Maffulli N, Del Buono A, Oliva F, Giai Via A, Frizziero A, Barazzuol M, et al. Muscle Injuries: A Brief Guide to Classification and Management. Transl Med Uni Sa 2015;12:14-8. https://doi.org/
11. Qaisar R, Bhaskaran S, Ranjit R, Sataranatarajan K, Premkumar P, Huseman K, et al. Restoration of SERCA ATPase prevents oxidative stress-related muscle atrophy and weakness. Redox Biol 2019;20:68-74. https://doi.org/10.1016/j.redox.2018.09.018.
12. Mah JK, Joseph JT. An Overview of Congenital Myopathies. Continuum (Minneap Minn). 2016;22(6, Muscle and Neuromuscular Junction Disorders):1932-53. https://doi.org/10.1212/CON.0000000000000404.
13. Minetto MA, Qaisar R, Agoni V, Motta G, Longa E, Miotti D, et al. Quantitative and qualitative adaptations of muscle fibers to glucocorticoids. Muscle Nerve 2015;52(4):631-9. https://doi.org/10.1002/mus.24572.
14. Tomaszewski M, Stepien KM, Tomaszewska J, Czuczwar SJ. Statin-induced myopathies. Pharmacol Rep 2011;63(4):859-66. https://doi.org/10.1016/s1734-1140(11)70601-6.
15. Qaisar R, Karim A, Elmoselhi AB. Muscle unloading: A comparison between spaceflight and ground-based models. Acta Physiol (Oxf) 2020;228(3):e13431. https://doi.org/10.1111/apha.13431.
16. Alamdari N, Toraldo G, Aversa Z, Smith I, Castillero E, Renaud G, et al. Loss of muscle strength during sepsis is in part regulated by glucocorticoids and is associated with reduced muscle fiber stiffness. Am J Physiol Regul Integr Comp Physiol 2012;303(10):R1090-9. https://doi.org/10.1152/ajpregu.00636.2011.
17. Maffei M, Longa E, Qaisar R, Agoni V, Desaphy JF, Camerino DC, et al. Actin sliding velocity on pure myosin isoforms from hindlimb unloaded mice. Acta Physiol (Oxf) 2014;212(4):316-29. https://doi.org/10.1111/apha.12320.
18. Qaisar R, Renaud G, Morine K, Barton ER, Sweeney HL, Larsson L. Is functional hypertrophy and specific force coupled with the addition of myonuclei at the single muscle fiber level? FASEB J 2012;26(3):1077-85. https://doi.org/10.1096/fj.11-192195.
19. Qaisar R, Larsson L. What determines myonuclear domain size? Indian J Physiol Pharmacol 2014;58(1):1-12. https://doi.org/
20. Aman F, El Khatib E, AlNeaimi A, Mohamed A, Almulla AS, Zaidan A, et al. Is the myonuclear domain ceiling hypothesis dead? Singapore Med J 2021. https://doi.org/10.11622/smedj.2021103.
21. Wang YX, Rudnicki MA. Satellite cells, the engines of muscle repair. Nat Rev Mol Cell Biol 2011;13(2):127-33. https://doi.org/10.1038/nrm3265.
22. McCarthy JJ, Mula J, Miyazaki M, Erfani R, Garrison K, Farooqui AB, et al. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle. Development 2011;138(17):3657-66. https://doi.org/10.1242/dev.068858.
23. Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, et al. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 2005;122(2):289-301. https://doi.org/10.1016/j.cell.2005.05.010.
24. Birbrair A, Zhang T, Wang ZM, Messi ML, Enikolopov GN, Mintz A, et al. Role of pericytes in skeletal muscle regeneration and fat accumulation. Stem Cells Dev 2013;22(16):2298-314. https://doi.org/10.1089/scd.2012.0647.
25. Pagano AF, Demangel R, Brioche T, Jublanc E, Bertrand-Gaday C, Candau R, et al. Muscle Regeneration with Intermuscular Adipose Tissue (IMAT) Accumulation Is Modulated by Mechanical Constraints. PLoS One 2015;10(12):e0144230. https://doi.org/10.1371/journal.pone.0144230.
26. Kobayashi K, Izawa T, Kuwamura M, Yamate J. Dysferlin and animal models for dysferlinopathy. J Toxicol Pathol 2012;25(2):135-47. https://doi.org/10.1293/tox.25.135.
27. He B, Tang RH, Weisleder N, Xiao B, Yuan Z, Cai C, et al. Enhancing muscle membrane repair by gene delivery of MG53 ameliorates muscular dystrophy and heart failure in delta-Sarcoglycan-deficient hamsters. Mol Ther 2012;20(4):727-35. https://doi.org/10.1038/mt.2012.5.
28. Weisleder N, Takeshima H, Ma J. Mitsugumin 53 (MG53) facilitates vesicle trafficking in striated muscle to contribute to cell membrane repair. Commun Integr Biol 2009;2(3):225-6. https://doi.org/10.4161/cib.2.3.8077.
29. Zhu H, Hou J, Roe JL, Park KH, Tan T, Zheng Y, et al. Amelioration of ischemia-reperfusion-induced muscle injury by the recombinant human MG53 protein. Muscle Nerve 2015;52(5):852-8. https://doi.org/10.1002/mus.24619.
30. Carmeille R, Bouvet F, Tan S, Croissant C, Gounou C, Mamchaoui K, et al. Membrane repair of human skeletal muscle cells requires Annexin-A5. Biochim Biophys Acta 2016;1863(9):2267-79. https://doi.org/10.1016/j.bbamcr.2016.06.003.
31. Demonbreun AR, Quattrocelli M, Barefield DY, Allen MV, Swanson KE, McNally EM. An actin-dependent annexin complex mediates plasma membrane repair in muscle. J Cell Biol 2016;213(6):705-18. https://doi.org/10.1083/jcb.201512022.
32. Munoz-Canoves P, Scheele C, Pedersen BK, Serrano AL. Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? FEBS J 2013;280(17):4131-48. https://doi.org/10.1111/febs.12338.
33. Lee JH, Jun HS. Role of Myokines in Regulating Skeletal Muscle Mass and Function. Front Physiol 2019;10:42. https://doi.org/10.3389/fphys.2019.00042.
34. Teixeira CF, Zamuner SR, Zuliani JP, Fernandes CM, Cruz-Hofling MA, Fernandes I, et al. Neutrophils do not contribute to local tissue damage, but play a key role in skeletal muscle regeneration, in mice injected with Bothrops asper snake venom. Muscle Nerve 2003;28(4):449-59. https://doi.org/10.1002/mus.10453.
35. Novak ML, Weinheimer-Haus EM, Koh TJ. Macrophage activation and skeletal muscle healing following traumatic injury. J Pathol 2014;232(3):344-55. https://doi.org/10.1002/path.4301.
36. Dort J, Fabre P, Molina T, Dumont NA. Macrophages Are Key Regulators of Stem Cells during Skeletal Muscle Regeneration and Diseases. Stem Cells Int 2019;2019:4761427. https://doi.org/10.1155/2019/4761427.
37. Chazaud B, Sonnet C, Lafuste P, Bassez G, Rimaniol AC, Poron F, et al. Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. J Cell Biol 2003;163(5):1133-43. https://doi.org/10.1083/jcb.200212046.
38. Merly F, Lescaudron L, Rouaud T, Crossin F, Gardahaut MF. Macrophages enhance muscle satellite cell proliferation and delay their differentiation. Muscle Nerve 1999;22(6):724-32. https://doi.org/10.1002/(sici)1097-4598(199906)22:6<724::aid-mus9>3.0.co;2-o.
39. Tidball JG, Wehling-Henricks M. Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol 2007;578(Pt 1):327-36. https://doi.org/10.1113/jphysiol.2006.118265.
40. Sack GH, Jr. Serum amyloid A - a review. Mol Med 2018;24(1):46. https://doi.org/10.1186/s10020-018-0047-0.
41. Ohtake Y, Tojo H, Seiki M. Multifunctional roles of MT1-MMP in myofiber formation and morphostatic maintenance of skeletal muscle. J Cell Sci 2006;119(Pt 18):3822-32. https://doi.org/10.1242/jcs.03158.