Incidence and Severity of Myofiber Branching with Regeneration and Aging

Overview

Journal Skelet Muscle

Specialty Physiology

Date 2014 May 24

PMID 24855558

Citations 37

Authors

Christophe Pichavant

Grace K Pavlath

Affiliations

Soon will be listed here.

Abstract

Background: Myofibers with an abnormal branching cytoarchitecture are commonly found in muscular dystrophy and in regenerated or aged nondystrophic muscles. Such branched myofibers from dystrophic mice are more susceptible to damage than unbranched myofibers in vitro, suggesting that muscles containing a high percentage of these myofibers are more prone to injury. Little is known about the regulation of myofiber branching.

Methods: To gain insights into the formation and fate of branched myofibers, we performed in-depth analyses of single myofibers isolated from dystrophic and nondystrophic (myotoxin-injured or aged) mouse muscles. The proportion of branched myofibers, the number of branches per myofiber and the morphology of the branches were assessed.

Results: Aged dystrophic mice exhibited the most severe myofiber branching as defined by the incidence of branched myofibers and the number of branches per myofiber, followed by myotoxin-injured, wild-type muscles and then aged wild-type muscles. In addition, the morphology of the branched myofibers differed among the various models. In response to either induced or ongoing muscle degeneration, branching was restricted to regenerated myofibers containing central nuclei. In myotoxin-injured muscles, the amount of branched myofibers remained stable over time.

Conclusion: We suggest that myofiber branching is a consequence of myofiber remodeling during muscle regeneration. Our present study lays valuable groundwork for identifying the molecular pathways leading to myofiber branching in dystrophy, trauma and aging. Decreasing myofiber branching in dystrophic patients may improve muscle resistance to mechanical stress.

Citing Articles

Intrinsic Muscle Stem Cell Dysfunction Contributes to Impaired Regeneration in the mdx Mouse.

Esper M, Brun C, Lin A, Feige P, Catenacci M, Sincennes M J Cachexia Sarcopenia Muscle. 2024; 16(1):e13682.

PMID: 39723578 PMC: 11669949. DOI: 10.1002/jcsm.13682.

Three-dimensional imaging studies in mice identify cellular dynamics of skeletal muscle regeneration.

Collins B, Shapiro J, Scheib M, Musci R, Verma M, Kardon G Dev Cell. 2024; 59(11):1457-1474.e5.

PMID: 38569550 PMC: 11153043. DOI: 10.1016/j.devcel.2024.03.017.

Hallmarks of ageing in human skeletal muscle and implications for understanding the pathophysiology of sarcopenia in women and men.

Granic A, Suetterlin K, Shavlakadze T, Grounds M, Sayer A Clin Sci (Lond). 2023; 137(22):1721-1751.

PMID: 37986616 PMC: 10665130. DOI: 10.1042/CS20230319.

Detyrosinated microtubule arrays drive myofibrillar malformations in muscle fibers.

Harriot A, Altair Morris T, Vanegas C, Kallenbach J, Pinto K, Joca H Front Cell Dev Biol. 2023; 11:1209542.

PMID: 37691825 PMC: 10485621. DOI: 10.3389/fcell.2023.1209542.

Regenerating Myofibers after an Acute Muscle Injury: What Do We Really Know about Them?.

Pizza F, Buckley K Int J Mol Sci. 2023; 24(16).

PMID: 37628725 PMC: 10454182. DOI: 10.3390/ijms241612545.

References

Yin H, Price F, Rudnicki M . Satellite cells and the muscle stem cell niche. Physiol Rev. 2013; 93(1):23-67. PMC: 4073943. DOI: 10.1152/physrev.00043.2011. View

Chan S, Head S . The role of branched fibres in the pathogenesis of Duchenne muscular dystrophy. Exp Physiol. 2011; 96(6):564-71. DOI: 10.1113/expphysiol.2010.056713. View

Blaivas M, Carlson B . Muscle fiber branching--difference between grafts in old and young rats. Mech Ageing Dev. 1991; 60(1):43-53. DOI: 10.1016/0047-6374(91)90108-c. View

Pavlath G . Spatial and functional restriction of regulatory molecules during mammalian myoblast fusion. Exp Cell Res. 2010; 316(18):3067-72. PMC: 2952734. DOI: 10.1016/j.yexcr.2010.05.025. View

Blaveri K, Heslop L, Yu D, Rosenblatt J, Gross J, Partridge T . Patterns of repair of dystrophic mouse muscle: studies on isolated fibers. Dev Dyn. 1999; 216(3):244-56. DOI: 10.1002/(SICI)1097-0177(199911)216:3<244::AID-DVDY3>3.0.CO;2-9. View

Abmayr S, Pavlath G . Myoblast fusion: lessons from flies and mice. Development. 2012; 139(4):641-56. PMC: 3265056. DOI: 10.1242/dev.068353. View

Griffin C, Kafadar K, Pavlath G . MOR23 promotes muscle regeneration and regulates cell adhesion and migration. Dev Cell. 2009; 17(5):649-61. PMC: 2780437. DOI: 10.1016/j.devcel.2009.09.004. View

Brown L, Lopez J, Olsen J, Rudel R, Simmons R, Taylor S . Branched skeletal muscle fibers not associated with dysfunction. Muscle Nerve. 1982; 5(8):645-53. DOI: 10.1002/mus.880050810. View

Boldrin L, Muntoni F, Morgan J . Are human and mouse satellite cells really the same?. J Histochem Cytochem. 2010; 58(11):941-55. PMC: 2958137. DOI: 10.1369/jhc.2010.956201. View

10.

Schmalbruch H . The morphology of regeneration of skeletal muscles in the rat. Tissue Cell. 1976; 8(4):673-92. DOI: 10.1016/0040-8166(76)90039-2. View

11.

Merrick D, Stadler L, Larner D, Smith J . Muscular dystrophy begins early in embryonic development deriving from stem cell loss and disrupted skeletal muscle formation. Dis Model Mech. 2009; 2(7-8):374-88. PMC: 2707105. DOI: 10.1242/dmm.001008. View

12.

Head S . Branched fibres in old dystrophic mdx muscle are associated with mechanical weakening of the sarcolemma, abnormal Ca2+ transients and a breakdown of Ca2+ homeostasis during fatigue. Exp Physiol. 2010; 95(5):641-56. DOI: 10.1113/expphysiol.2009.052019. View

13.

Hurme T, Kalimo H . Adhesion in skeletal muscle during regeneration. Muscle Nerve. 1992; 15(4):482-9. DOI: 10.1002/mus.880150412. View

14.

Schott G, McArdle B . Barium-induced skeletal muscle paralysis in the rat, and its relationship to human familial periodic paralysis. J Neurol Neurosurg Psychiatry. 1974; 37(1):32-9. PMC: 494560. DOI: 10.1136/jnnp.37.1.32. View

15.

Caldwell C, Mattey D, Weller R . Role of the basement membrane in the regeneration of skeletal muscle. Neuropathol Appl Neurobiol. 1990; 16(3):225-38. DOI: 10.1111/j.1365-2990.1990.tb01159.x. View

16.

Bushby K, Finkel R, Birnkrant D, Case L, Clemens P, Cripe L . Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2009; 9(1):77-93. DOI: 10.1016/S1474-4422(09)70271-6. View

17.

Shi X, Garry D . Muscle stem cells in development, regeneration, and disease. Genes Dev. 2006; 20(13):1692-708. DOI: 10.1101/gad.1419406. View

18.

Bray G, BANKER B . An ultrastructural study of degeneration and necrosis of muscle in the dystrophic mouse. Acta Neuropathol. 1970; 15(1):34-44. DOI: 10.1007/BF00690687. View

19.

Wallace G, McNally E . Mechanisms of muscle degeneration, regeneration, and repair in the muscular dystrophies. Annu Rev Physiol. 2008; 71:37-57. DOI: 10.1146/annurev.physiol.010908.163216. View

20.

Goodman C, Frey J, Mabrey D, Jacobs B, Lincoln H, You J . The role of skeletal muscle mTOR in the regulation of mechanical load-induced growth. J Physiol. 2011; 589(Pt 22):5485-501. PMC: 3240886. DOI: 10.1113/jphysiol.2011.218255. View