Skeletal muscle: molecular structure, myogenesis, biological functions, and diseases

Abstract

Skeletal muscle is an important motor organ with multinucleated myofibers as its smallest cellular units. Myofibers are formed after undergoing cell differentiation, cell–cell fusion, myonuclei migration, and myofibril crosslinking among other processes and undergo morphological and functional changes or lesions after being stimulated by internal or external factors. The above processes are collectively referred to as myogenesis. After myofibers mature, the function and behavior of skeletal muscle are closely related to the voluntary movement of the body. In this review, we systematically and comprehensively discuss the physiological and pathological processes associated with skeletal muscles from five perspectives: molecule basis, myogenesis, biological function, adaptive changes, and myopathy. In the molecular structure and myogenesis sections, we gave a brief overview, focusing on skeletal muscle-specific fusogens and nuclei-related behaviors including cell–cell fusion and myonuclei localization. Subsequently, we discussed the three biological functions of skeletal muscle (muscle contraction, thermogenesis, and myokines secretion) and its response to stimulation (atrophy, hypertrophy, and regeneration), and finally settled on myopathy. In general, the integration of these contents provides a holistic perspective, which helps to further elucidate the structure, characteristics, and functions of skeletal muscle.

Keywords

biological function / myogenesis / myonuclear / myopathy / skeletal muscle

References

1	X Wang, J Vannier, X Yang, et al. Muscle systems and motility of early animals highlighted by cnidarians from the basal Cambrian. Elife. 2022:11.
2	AG Liu, JJ Matthews, LR Menon, D McIlroy, MD Brasier. Haootia quadriformis n. gen., n. sp., interpreted as a muscular cnidarian impression from the Late Ediacaran period (approx. 560 Ma). Proc Biol Sci. 2014;281(1793).
3	M Murphy, G Kardon. Origin of vertebrate limb muscle: the role of progenitor and myoblast populations. Curr Top Dev Biol. 2011;96:1-32.
4	J Chal, O Pourquié. Making muscle: skeletal myogenesis in vivo and in vitro. Development. 2017;144(12):2104-2122.
5	E Leikina, DG Gamage, V Prasad, et al. Myomaker and Myomerger work independently to control distinct steps of membrane remodeling during myoblast fusion. Dev Cell. 2018;46(6):767-780. e7.
6	BR Berridge, JF Van Vleet, E Herman. Chapter 46 - Cardiac, Vascular, and Skeletal Muscle Systems. In: Haschek WM, Rousseaux CG, Wallig MA, eds. Haschek and Rousseaux's Handbook of Toxicologic Pathology (Third Edition). Academic Press; 2013:1567-1665.
7	SV Brooks, SD Guzman, LP Ruiz. Skeletal muscle structure, physiology, and function. Handb Clin Neurol. 2023;195:3-16.
8	R Sartori, V Romanello, M Sandri. Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun. 2021;12(1):330.
9	S Schiaffino, KA Dyar, S Ciciliot, B Blaauw, M Sandri. Mechanisms regulating skeletal muscle growth and atrophy. Febs J. 2013;280(17):4294-4314.
10	LAD Silva, CRM Malfatti, KCN Soares, MCD Silva, MR Brasil. Unraveling the interplay of oxidative stress, aging, and skeletal muscle: insights and interventions for optimal muscle function in the elderly. J Adv Med Med Res. 2023;35(15):21-27.
11	Q Goh, DP Millay. Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy. Elife. 2017:6.
12	DP Millay, JR O'Rourke, LB Sutherland, et al. Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature. 2013;499(7458):301-305.
13	P Bi, A Ramirez-Martinez, H Li, et al. Control of muscle formation by the fusogenic micropeptide myomixer. Science. 2017;356(6335):323-327.
14	ME Quinn, Q Goh, M Kurosaka, et al. Myomerger induces fusion of non-fusogenic cells and is required for skeletal muscle development. Nat Commun. 2017;8:15665.
15	Q Zhang, AA Vashisht, J O'Rourke, et al. The microprotein Minion controls cell fusion and muscle formation. Nat Commun. 2017;8:15664.
16	CA Henderson, CG Gomez, SM Novak, L Mi-Mi, CC Gregorio. Overview of the muscle cytoskeleton. Compr Physiol. 2017;7(3):891-944.
17	N Segev, O Avinoam, B Podbilewicz. Fusogens. Curr Biol. 2018;28(8):R378-r380.
18	A Landemaine, A Ramirez-Martinez, O Monestier, et al. Trout myomaker contains 14 minisatellites and two sequence extensions but retains fusogenic function. J Biol Chem. 2019;294(16):6364-6374.
19	A Landemaine, PY Rescan, JC Gabillard. Myomaker mediates fusion of fast myocytes in zebrafish embryos. Biochem Biophys Res Commun. 2014;451(4):480-484.
20	W Zhang, S Roy. Myomaker is required for the fusion of fast-twitch myocytes in the zebrafish embryo. Dev Biol. 2017;423(1):24-33.
21	W Luo, E Li, Q Nie, X Zhang. Myomaker, regulated by MYOD, MYOG and miR-140-3p, promotes chicken myoblast fusion. Int J Mol Sci. 2015;16(11):26186-26201.
22	Y Huang, S Wu, J Zhang, H Wen, M Zhang, F He. Methylation status and expression patterns of myomaker gene play important roles in postnatal development in the Japanese flounder (Paralichthys olivaceus). Gen Comp Endocrinol. 2019;280:104-114.
23	DP Millay, DG Gamage, ME Quinn, et al. Structure-function analysis of myomaker domains required for myoblast fusion. Proc Natl Acad Sci USA. 2016;113(8):2116-2121.
24	DG Gamage, E Leikina, ME Quinn, A Ratinov, LV Chernomordik, DP Millay. Insights into the localization and function of myomaker during myoblast fusion. J Biol Chem. 2017;292(42):17272-17289.
25	MJ Petrany, T Song, S Sadayappan, DP Millay. Myocyte-derived Myomaker expression is required for regenerative fusion but exacerbates membrane instability in dystrophic myofibers. JCI Insight. 2020;5(9).
26	P Wu, P Yong, Z Zhang, et al. Loss of Myomixer results in defective myoblast fusion, impaired muscle growth, and severe myopathy in zebrafish. Mar Biotechnol (NY). 2022;24(5):1023-1038.
27	J Shi, P Bi, J Pei, et al. Requirement of the fusogenic micropeptide myomixer for muscle formation in zebrafish. Proc Natl Acad Sci USA. 2017;114(45):11950-11955.
28	M Perello-Amoros, C Rallière, J Gutiérrez, JC Gabillard. Myomixer is expressed during embryonic and post-larval hyperplasia, muscle regeneration and differentiation of myoblats in rainbow trout (Oncorhynchus mykiss). Gene. 2021;790:145688.
29	M Perelló-Amorós, A Otero-Tarrazón, V Jorge-Pedraza, et al. Myomaker and Myomixer characterization in Gilthead Sea Bream under different myogenesis conditions. Int J Mol Sci. 2022;23(23).
30	P Bi, JR McAnally, JM Shelton, E Sánchez-Ortiz, R Bassel-Duby, EN Olson. Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration. Proc Natl Acad Sci USA. 2018;115(15):3864-3869.
31	DG Gamage, K Melikov, P Munoz-Tello, et al. Phosphatidylserine orchestrates Myomerger membrane insertions to drive myoblast fusion. Proc Natl Acad Sci USA. 2022;119(38):e2202490119.
32	PC Witcher, C Sun, DP Millay. Expression of Myomaker and Myomerger in myofibers causes muscle pathology. Skelet Muscle. 2023;13(1):8.
33	DP Millay, LB Sutherland, R Bassel-Duby, EN Olson. Myomaker is essential for muscle regeneration. Genes Dev. 2014;28(15):1641-1646.
34	M Ganassi, S Badodi, HP Ortuste Quiroga, PS Zammit, Y Hinits, SM Hughes. Myogenin promotes myocyte fusion to balance fibre number and size. Nat Commun. 2018;9(1):4232.
35	J Esteves de Lima, C Blavet, MA Bonnin, et al. TMEM8C-mediated fusion is regionalized and regulated by NOTCH signalling during foetal myogenesis. Development. 2022;149(2).
36	J He, F Wang, P Zhang, et al. miR-491 inhibits skeletal muscle differentiation through targeting myomaker. Arch Biochem Biophys. 2017;625-626:30-38.
37	J Ma, Y Zhu, X Zhou, et al. miR-205 regulates the fusion of porcine myoblast by targeting the Myomaker gene. Cells. 2023;12(8).
38	KC Zhu, BS Liu, HY Guo, et al. Functional analysis of two MyoDs revealed their role in the activation of myomixer expression in yellowfin seabream (Acanthopagrus latus) (Hottuyn, 1782). Int J Biol Macromol. 2020;156:1081-1090.
39	JH Yang, MW Chang, D Tsitsipatis, et al. LncRNA OIP5-AS1-directed miR-7 degradation promotes MYMX production during human myogenesis. Nucleic Acids Res. 2022;50(12):7115-7133.
40	M Yamamoto, NP Legendre, AA Biswas, et al. Loss of MyoD and Myf5 in skeletal muscle stem cells results in altered myogenic programming and failed regeneration. Stem Cell Rep. 2018;10(3):956-969.
41	H Zhang, J Wen, A Bigot, et al. Human myotube formation is determined by MyoD-Myomixer/Myomaker axis. Sci Adv. 2020;6(51).
42	A Adhikari, W Kim, J Davie. Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation. PLoS One. 2021;16(1):e0245618.
43	V Salizzato, S Zanin, C Borgo, et al. Protein kinase CK2 subunits exert specific and coordinated functions in skeletal muscle differentiation and fusogenic activity. Faseb J. 2019;33(10):10648-10667.
44	DW Hammers, CC Hart, MK Matheny, et al. Filopodia powered by class x myosin promote fusion of mammalian myoblasts. Elife. 2021:10.
45	A Tasca, K Astleford, A Lederman, et al. Regulation of osteoclast differentiation by myosin X. Sci Rep. 2017;7(1):7603.
46	V Horsley, KM Jansen, ST Mills, GK Pavlath. IL-4 acts as a myoblast recruitment factor during mammalian muscle growth. Cell. 2003;113(4):483-494.
47	M Kurosaka, YL Hung, S Machida, K Kohda. IL-4 signaling promotes myoblast differentiation and fusion by enhancing the expression of MyoD, Myogenin, and Myomerger. Cells. 2023;12(9).
48	B Chen, W You, T Shan. Myomaker, and Myomixer-Myomerger-Minion modulate the efficiency of skeletal muscle development with melatonin supplementation through Wnt/β-catenin pathway. Exp Cell Res. 2019;385(2):111705.
49	Y Sun, S Zhan, S Zhao, et al. HuR promotes the differentiation of goat skeletal muscle satellite cells by regulating Myomaker mRNA stability. Int J Mol Sci. 2023;24(8).
50	Ortuste Quiroga HP, M Ganassi, S Yokoyama, et al. Fine-tuning of Piezo1 expression and activity ensures efficient myoblast fusion during skeletal myogenesis. Cells. 2022;11(3).
51	TH Youm, SH Woo, ES Kwon, SS Park. NADPH oxidase 4 contributes to myoblast fusion and skeletal muscle regeneration. Oxid Med Cell Longev. 2019;2019:3585390.
52	Z Wu, H Xu, Y Xu, et al. Andrographolide promotes skeletal muscle regeneration after acute injury through epigenetic modulation. Eur J Pharmacol. 2020;888:173470.
53	X Zhong, QQ Wang, JW Li, YM Zhang, XR An, J Hou. Ten-eleven translocation-2 (Tet2) is involved in myogenic differentiation of skeletal myoblast cells in vitro. Sci Rep. 2017;7:43539.
54	L Gong, X Zhang, K Qiu, L He, Y Wang, J Yin. Arginine promotes myogenic differentiation and myotube formation through the elevation of cytoplasmic calcium concentration. Anim Nutr. 2021;7(4):1115-1123.
55	T Hosoyama, H Iida, M Kawai-Takaishi, K Watanabe. Vitamin D inhibits myogenic cell fusion and expression of fusogenic genes. Nutrients. 2020;12(8).
56	SM van den Eijnde, MJ van den Hoff, CP Reutelingsperger, et al. Transient expression of phosphatidylserine at cell-cell contact areas is required for myotube formation. J Cell Sci. 2001;114(20):3631-3642. Pt.
57	AE Hochreiter-Hufford, CS Lee, JM Kinchen, et al. Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature. 2013;497(7448):263-267.
58	SY Park, Y Yun, JS Lim, et al. Stabilin-2 modulates the efficiency of myoblast fusion during myogenic differentiation and muscle regeneration. Nat Commun. 2016;7:10871.
59	J Gros, M Manceau, V Thomé, C Marcelle. A common somitic origin for embryonic muscle progenitors and satellite cells. Nature. 2005;435(7044):954-958.
60	P Seale, LA Sabourin, A Girgis-Gabardo, A Mansouri, P Gruss, MA Rudnicki. Pax7 is required for the specification of myogenic satellite cells. Cell. 2000;102(6):777-786.
61	S Kuang, K Kuroda, F Le Grand, MA Rudnicki. Asymmetric self-renewal and commitment of satellite stem cells in muscle. Cell. 2007;129(5):999-1010.
62	JF Bachman, RS Blanc, ND Paris, et al. Radiation-induced damage to prepubertal Pax7+ skeletal muscle stem cells drives lifelong deficits in myofiber size and nuclear number. iScience. 2020;23(11):101760.
63	S Deng, M Azevedo, M Baylies. Acting on identity: myoblast fusion and the formation of the syncytial muscle fiber. Semin Cell Dev Biol. 2017;72:45-55.
64	L Lehka, MJ R?dowicz. Mechanisms regulating myoblast fusion: a multilevel interplay. Semin Cell Dev Biol. 2020;104:81-92.
65	Y Mitani, RJ Vagnozzi, DP Millay. In vivo myomaker-mediated heterologous fusion and nuclear reprogramming. Faseb J. 2017;31(1):400-411.
66	G Golani, E Leikina, K Melikov, et al. Myomerger promotes fusion pore by elastic coupling between proximal membrane leaflets and hemifusion diaphragm. Nat Commun. 2021;12(1):495.
67	M Chakraborty, A Sivan, A Biswas, B Sinha. Early tension regulation coupled to surface myomerger is necessary for the primary fusion of C2C12 myoblasts. Front Physiol. 2022:13.
68	JC Bruusgaard, K Liest?l, M Ekmark, K Kollstad, K Gundersen. Number and spatial distribution of nuclei in the muscle fibres of normal mice studied in vivo. J Physiol. 2003;551(2):467-478. Pt.
69	MA Collins, TR Mandigo, JM Camuglia, et al. Emery-Dreifuss muscular dystrophy-linked genes and centronuclear myopathy-linked genes regulate myonuclear movement by distinct mechanisms. Mol Biol Cell. 2017;28(17):2303-2317.
70	M Azevedo, MK Baylies. Getting into position: nuclear movement in muscle cells. Trends Cell Biol. 2020;30(4):303-316.
71	JR Padilla, LM Ferreira, ES Folker. Nuclear movement in multinucleated cells. Development. 2022;149(21).
72	B Cadot, V Gache, E Vasyutina, S Falcone, C Birchmeier, ER Gomes. Nuclear movement during myotube formation is microtubule and dynein dependent and is regulated by Cdc42, Par6 and Par3. EMBO Rep. 2012;13(8):741-749.
73	J Liu, ZP Huang, M Nie, et al. Regulation of myonuclear positioning and muscle function by the skeletal muscle-specific CIP protein. Proc Natl Acad Sci USA. 2020;117(32):19254-19265.
74	T Metzger, V Gache, M Xu, et al. MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function. Nature. 2012;484(7392):120-124.
75	B Cadot, V Gache, ER Gomes. Moving and positioning the nucleus in skeletal muscle—one step at a time. Nucleus. 2015;6(5):373-381.
76	MH Wilson, EL Holzbaur. Nesprins anchor kinesin-1 motors to the nucleus to drive nuclear distribution in muscle cells. Development. 2015;142(1):218-228.
77	S De Silva, Z Fan, B Kang, CM Shanahan, Q Zhang. Nesprin-1: novel regulator of striated muscle nuclear positioning and mechanotransduction. Biochem Soc Trans. 2023;51(3):1331-1345.
78	ES Folker, VK Schulman, MK Baylies. Muscle length and myonuclear position are independently regulated by distinct Dynein pathways. Development. 2012;139(20):3827-3837.
79	Y Zhao, S Oten, A Yildiz. Nde1 promotes Lis1-mediated activation of dynein. Nat Commun. 2023;14(1):7221.
80	VK Schulman, ES Folker, JN Rosen, MK Baylies. Syd/JIP3 and JNK signaling are required for myonuclear positioning and muscle function. PLoS Genet. 2014;10(12):e1004880.
81	AL Auld, SA Roberts, CB Murphy, JM Camuglia, ES Folker. Aplip1, the Drosophila homolog of JIP1, regulates myonuclear positioning and muscle stability. J Cell Sci. 2018;131(6).
82	W Roman, JP Martins, FA Carvalho, et al. Myofibril contraction and crosslinking drive nuclear movement to the periphery of skeletal muscle. Nat Cell Biol. 2017;19(10):1189-1201.
83	W Roman, JP Martins, ER Gomes. Local arrangement of fibronectin by myofibroblasts governs peripheral nuclear positioning in muscle cells. Dev Cell. 2018;46(1):102-111. e6.
84	N Osmani, N Vitale, JP Borg. Etienne-Manneville S. Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Curr Biol. 2006;16(24):2395-2405.
85	KA Hansson, E Eftest?l, JC Bruusgaard, et al. Myonuclear content regulates cell size with similar scaling properties in mice and humans. Nat Commun. 2020;11(1):6288.
86	IA Johnston, M Abercromby, O Andersen. Muscle fibre number varies with haemoglobin phenotype in Atlantic cod as predicted by the optimal fibre number hypothesis. Biol Lett. 2006;2(4):590-592.
87	AG Jimenez, RM Dillaman, ST Kinsey. Large fibre size in skeletal muscle is metabolically advantageous. Nat Commun. 2013;4:2150.
88	JK Petrella, JS Kim, DL Mayhew, JM Cross, MM Bamman. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis. J Appl Physiol (1985). 2008;104(6):1736-1742.
89	T Snijders, JS Smeets, J van Kranenburg, AK Kies, LJ van Loon, LB Verdijk. Changes in myonuclear domain size do not precede muscle hypertrophy during prolonged resistance-type exercise training. Acta Physiol (Oxf). 2016;216(2):231-239.
90	AAW Cramer, V Prasad, E Eftest?l, et al. Nuclear numbers in syncytial muscle fibers promote size but limit the development of larger myonuclear domains. Nat Commun. 2020;11(1):6287.
91	AA Cutler, JB Jackson, AH Corbett, GK Pavlath. Non-equivalence of nuclear import among nuclei in multinucleated skeletal muscle cells. J Cell Sci. 2018;131(3).
92	KA Murach, CM Dungan, F von Walden, Y Wen. Epigenetic evidence for distinct contributions of resident and acquired myonuclei during long-term exercise adaptation using timed in vivo myonuclear labeling. Am J Physiol Cell Physiol. 2022;322(1):C86-c93.
93	MJ Petrany, CO Swoboda, C Sun, et al. Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers. Nat Commun. 2020;11(1):6374.
94	K Mukund, S Subramaniam. Skeletal muscle: a review of molecular structure and function, in health and disease. Wiley Interdiscip Rev Syst Biol Med. 2020;12(1):e1462.
95	JD Powers, SA Malingen, M Regnier, TL Daniel. The sliding filament theory since Andrew Huxley: multiscale and multidisciplinary muscle research. Annu Rev Biophys. 2021;50:373-400.
96	AO Adewale, YH Ahn. Titin N2A domain and its interactions at the sarcomere. Int J Mol Sci. 2021;22(14).
97	K Maruyama. Connectin, an elastic protein from myofibrils. J Biochem. 1976;80(2):405-407.
98	K Wang. Purification of titin and nebulin. Methods Enzymol. 1982;85:264-274. Pt B.
99	Z Wang, M Grange, S Pospich, et al. Structures from intact myofibrils reveal mechanism of thin filament regulation through nebulin. Science. 2022;375(6582):eabn1934.
100	L Al-Qusairi, J Laporte. T-tubule biogenesis and triad formation in skeletal muscle and implication in human diseases. Skelet Muscle. 2011;1(1):26.
101	WR Frontera, J Ochala. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015;96(3):183-195.
102	S Schiaffino, C Reggiani. Fiber types in mammalian skeletal muscles. Physiol Rev. 2011;91(4):1447-1531.
103	Z Yan, M Okutsu, YN Akhtar, VA Lira. Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle. J Appl Physiol (1985). 2011;110(1):264-274.
104	RF Mancilla, L Lindeboom, L Grevendonk, et al. Skeletal muscle mitochondrial inertia is associated with carnitine acetyltransferase activity and physical function in humans. JCI Insight. 2023;8(1).
105	M Hargreaves, LL Spriet. Skeletal muscle energy metabolism during exercise. Nat Metab. 2020;2(9):817-828.
106	E Ozawa. Regulation of phosphorylase kinase by low concentrations of Ca ions upon muscle contraction: the connection between metabolism and muscle contraction and the connection between muscle physiology and Ca-dependent signal transduction. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(8):486-508.
107	JM Argilés, N Campos, JM Lopez-Pedrosa, R Rueda, L Rodriguez-Ma?as. Skeletal muscle regulates metabolism via interorgan crosstalk: roles in health and disease. J Am Med Dir Assoc. 2016;17(9):789-796.
108	EA Richter, M Hargreaves. Exercise, GLUT4, and skeletal muscle glucose uptake. Physiol Rev. 2013;93(3):993-1017.
109	JF Vigh-Larsen, N ?rtenblad, LL Spriet, K Overgaard, M Mohr. Muscle glycogen metabolism and high-intensity exercise performance: a narrative review. Sports Med. 2021;51(9):1855-1874.
110	M Periasamy, JL Herrera, FCG Reis. Skeletal muscle thermogenesis and its role in whole body energy metabolism. Diabetes Metab J. 2017;41(5):327-336.
111	H Li, C Wang, L Li, L Li. Skeletal muscle non-shivering thermogenesis as an attractive strategy to combat obesity. Life Sci. 2021;269:119024.
112	NC Bal, SK Sahoo, SK Maurya, M Periasamy. The role of sarcolipin in muscle non-shivering thermogenesis. Front Physiol. 2018;9:1217.
113	SK Maurya, NC Bal, DH Sopariwala, et al. Sarcolipin is a key determinant of the basal metabolic rate, and its overexpression enhances energy expenditure and resistance against diet-induced obesity. J Biol Chem. 2015;290(17):10840-10849.
114	BK Pedersen, A Steensberg, C Fischer, et al. Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil. 2003;24(2-3):113-119.
115	SM Barbalho, EV Prado Neto, R De Alvares Goulart, et al. Myokines: a descriptive review. J Sports Med Phys Fitness. 2020;60(12):1583-1590.
116	JH Lee, HS Jun. Role of myokines in regulating skeletal muscle mass and function. Front Physiol. 2019;10:42.
117	HY Moon, A Becke, D Berron, et al. Running-induced systemic cathepsin b secretion is associated with memory function. Cell Metab. 2016;24(2):332-340.
118	CD Wrann, JP White, J Salogiannnis, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013;18(5):649-659.
119	K Fosgerau, P Galle, T Hansen, et al. Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes. J Endocrinol. 2010;204(3):265-273.
120	F Norheim, TM Langleite, M Hjorth, et al. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. Febs J. 2014;281(3):739-749.
121	MCK Severinsen, BK Pedersen. Muscle-organ crosstalk: the emerging roles of myokines. Endocr Rev. 2020;41(4):594-609.
122	B Guo, ZK Zhang, C Liang, et al. Molecular communication from skeletal muscle to bone: a review for muscle-derived myokines regulating bone metabolism. Calcif Tissue Int. 2017;100(2):184-192.
123	S Schiaffino, C Reggiani, T Akimoto, B Blaauw. Molecular mechanisms of skeletal muscle hypertrophy. J Neuromuscul Dis. 2021;8(2):169-183.
124	X Li, Y Zhu, H Zhang, et al. MicroRNA-106a-5p inhibited C2C12 myogenesis via targeting PIK3R1 and modulating the PI3K/AKT signaling. Genes (Basel). 2018;9(7).
125	L Yin, N Li, W Jia, et al. Skeletal muscle atrophy: from mechanisms to treatments. Pharmacol Res. 2021;172:105807.
126	EA Nunes, T Stokes, J McKendry, BS Currier, SM Phillips. Disuse-induced skeletal muscle atrophy in disease and nondisease states in humans: mechanisms, prevention, and recovery strategies. Am J Physiol Cell Physiol. 2022;322(6):C1068.
127	BT Wall, T Snijders, JM Senden, et al. Disuse impairs the muscle protein synthetic response to protein ingestion in healthy men. J Clin Endocrinol Metab. 2013;98(12):4872-4881.
128	SC Bodine, E Latres, S Baumhueter, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001;294(5547):1704-1708.
129	PK Paul, S Bhatnagar, V Mishra, et al. The E3 ubiquitin ligase TRAF6 intercedes in starvation-induced skeletal muscle atrophy through multiple mechanisms. Mol Cell Biol. 2012;32(7):1248-1259.
130	SC Bodine, TN Stitt, M Gonzalez, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol. 2001;3(11):1014-1019.
131	C Rommel, SC Bodine, BA Clarke, et al. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol. 2001;3(11):1009-1013.
132	JJ McCarthy, J Mula, M Miyazaki, et al. Effective fiber hypertrophy in satellite cell-depleted skeletal muscle. Development. 2011;138(17):3657-3666.
133	TJ Kirby, RM Patel, TS McClintock, EE Dupont-Versteegden, CA Peterson, JJ McCarthy. Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy. Mol Biol Cell. 2016;27(5):788-798.
134	KA Murach, SH White, Y Wen, et al. Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice. Skelet Muscle. 2017;7(1):14.
135	SH Kook, YO Son, KC Choi, et al. Cyclic mechanical stress suppresses myogenic differentiation of adult bovine satellite cells through activation of extracellular signal-regulated kinase. Mol Cell Biochem. 2008;309(1-2):133-141.
136	ER Hunt, AL Confides, SM Abshire, EE Dupont-Versteegden, TA Butterfield. Massage increases satellite cell number independent of the age-associated alterations in sarcolemma permeability. Physiol Rep. 2019;7(17):e14200.
137	AC Wozniak, JE Anderson. The dynamics of the nitric oxide release-transient from stretched muscle cells. Int J Biochem Cell Biol. 2009;41(3):625-631.
138	A Pisconti, S Brunelli, M Di Padova, et al. Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion. J Cell Biol. 2013;200(3):359.
139	AL Serrano, B Baeza-Raja, E Perdiguero, M Jardí, P Mu?oz-Cánoves. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy. Cell Metab. 2008;7(1):33-44.
140	P Tavi, T Korhonen, SL H?nninen, et al. Myogenic skeletal muscle satellite cells communicate by tunnelling nanotubes. J Cell Physiol. 2010;223(2):376-383.
141	C Noviello, K Kobon, L Delivry, et al. RhoA within myofibers controls satellite cell microenvironment to allow hypertrophic growth. iScience. 2022;25(1):103616.
142	BD Peck, KA Murach, RG Walton, et al. A muscle cell-macrophage axis involving matrix metalloproteinase 14 facilitates extracellular matrix remodeling with mechanical loading. Faseb j. 2022;36(2):e22155.
143	S Zhou, W Zhang, G Cai, et al. Myofiber necroptosis promotes muscle stem cell proliferation via releasing Tenascin-C during regeneration. Cell Res. 2020;30(12):1063-1077.
144	Y Tsuchiya, Y Kitajima, H Masumoto, Y Ono. Damaged myofiber-derived metabolic enzymes act as activators of muscle satellite cells. Stem Cell Rep. 2020;15(4):926-940.
145	M Segawa, S Fukada, Y Yamamoto, et al. Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis. Exp Cell Res. 2008;314(17):3232-3244.
146	M Saclier, H Yacoub-Youssef, AL Mackey, et al. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration. Stem Cells. 2013;31(2):384-396.
147	B Chazaud, C Sonnet, P Lafuste, 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):1133-1143.
148	M Girgenrath, S Weng, CA Kostek, et al. TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration. Embo j. 2006;25(24):5826-5839.
149	H Du, CH Shih, MN Wosczyna, et al. Macrophage-released ADAMTS1 promotes muscle stem cell activation. Nat Commun. 2017;8(1):669.
150	T Varga, R Mounier, A Patsalos, et al. Macrophage PPARγ, a lipid activated transcription factor controls the growth factor GDF3 and skeletal muscle regeneration. Immunity. 2016;45(5):1038-1051.
151	A Patsalos, L Halasz, MA Medina-Serpas, et al. A growth factor-expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15. J Exp Med. 2022;219(1).
152	LC Ceafalan, TE Fertig, AC Popescu, BO Popescu, ME Hinescu, M Gherghiceanu. Skeletal muscle regeneration involves macrophage-myoblast bonding. Cell Adh Migr. 2018;12(3):228-235.
153	AP Kann, M Hung, RS Krauss. Cell-cell contact and signaling in the muscle stem cell niche. Curr Opin Cell Biol. 2021;73:78-83.
154	B Biferali, D Proietti, C Mozzetta, L Madaro. Fibro-adipogenic progenitors cross-talk in skeletal muscle: the social network. Front Physiol. 2019;10:1074.
155	A Ocampo, P Reddy, P Martinez-Redondo, et al. In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell. 2016;167(7):1719-1733. e12.
156	C Wang, R Rabadan Ros, P Martinez-Redondo, et al. In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche. Nat Commun. 2021;12(1):3094.
157	SI Fukada, T Higashimoto, A Kaneshige. Differences in muscle satellite cell dynamics during muscle hypertrophy and regeneration. Skelet Muscle. 2022;12(1):17.
158	S Fukuda, A Kaneshige, T Kaji, et al. Sustained expression of HeyL is critical for the proliferation of muscle stem cells in overloaded muscle. Elife. 2019:8.
159	SI Fukada, T Akimoto, A Sotiropoulos. Role of damage and management in muscle hypertrophy: different behaviors of muscle stem cells in regeneration and hypertrophy. Biochim Biophys Acta Mol Cell Res. 2020;1867(9):118742.
160	AA Cutler, B Pawlikowski, JR Wheeler, et al. The regenerating skeletal muscle niche drives satellite cell return to quiescence. iScience. 2022;25(6):104444.
161	IM Conboy, MJ Conboy, GM Smythe, TA Rando. Notch-mediated restoration of regenerative potential to aged muscle. Science. 2003;302(5650):1575-1577.
162	AS Brack, MJ Conboy, S Roy, et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007;317(5839):807-810.
163	ME Carlson, M Hsu, IM Conboy. Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells. Nature. 2008;454(7203):528-532.
164	FD Price, J von Maltzahn, CF Bentzinger, et al. Inhibition of JAK-STAT signaling stimulates adult satellite cell function. Nat Med. 2014;20(10):1174-1181.
165	JV Chakkalakal, KM Jones, MA Basson, AS Brack. The aged niche disrupts muscle stem cell quiescence. Nature. 2012;490(7420):355-360.
166	P Sousa-Victor, S Gutarra, L García-Prat, et al. Geriatric muscle stem cells switch reversible quiescence into senescence. Nature. 2014;506(7488):316-321.
167	P Bottoni, G Gionta, R Scatena. Remarks on mitochondrial myopathies. Int J Mol Sci. 2022;24(1).
168	KN North, CH Wang, N Clarke, et al. Approach to the diagnosis of congenital myopathies. Neuromuscul Disord. 2014;24(2):97-116.
169	MA Tarnopolsky. Metabolic myopathies. Continuum (Minneap Minn). 2022;28(6):1752-1777.
170	JR Trivedi. Muscle channelopathies. Continuum (Minneap Minn). 2022;28(6):1778-1799.
171	E Mercuri, CG B?nnemann, F Muntoni. Muscular dystrophies. Lancet. 2019;394(10213):2025-2038.
172	JJ Dowling, CC Weihl, MJ Spencer. Molecular and cellular basis of genetically inherited skeletal muscle disorders. Nat Rev Mol Cell Biol. 2021;22(11):713-732.
173	Y Allenbach, O Benveniste. Acquired necrotizing myopathies. Curr Opin Neurol. 2013;26(5):554-560.
174	JC Carey, RM Fineman, FA Ziter. The Robin sequence as a consequence of malformation, dysplasia, and neuromuscular syndromes. J Pediatr. 1982;101(5):858-864.
175	A Camacho, B Martínez, S Alvarez, et al. Carey-Fineman-Ziter syndrome: a MYMK-related myopathy mimicking brainstem dysgenesis. J Neuromuscul Dis. 2020;7(3):309-313.
176	C Hedberg-Oldfors, C Lindberg, A Oldfors. Carey-Fineman-Ziter syndrome with mutations in the myomaker gene and muscle fiber hypertrophy. Neurol Genet. 2018;4(4):e254.
177	SA Di Gioia, S Connors, N Matsunami, et al. A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome. Nat Commun. 2017;8:16077.
178	A Ramirez-Martinez, Y Zhang, MJ van den Boogaard, et al. Impaired activity of the fusogenic micropeptide Myomixer causes myopathy resembling Carey-Fineman-Ziter syndrome. J Clin Invest. 2022;132(11).
179	NM McCormack, E Villalón, C Viollet, et al. Survival motor neuron deficiency slows myoblast fusion through reduced myomaker and myomixer expression. J Cachexia Sarcopenia Muscle. 2021;12(4):1098-1116.
180	M Pavli?ev, GP Wagner. The value of broad taxonomic comparisons in evolutionary medicine: disease is not a trait but a state of a trait!. MedComm(2020). 2022;3(4):e174.
181	R Duncan. Fusogenic reoviruses and their fusion-associated small transmembrane (FAST) proteins. Annu Rev Virol. 2019;6(1):341-363.
182	SM Hindi, MJ Petrany, E Greenfeld, et al. Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery. Cell. 2023;186(10):2062-2077. e17.
183	R Gómez-Oca, BS Cowling, J Laporte. Common pathogenic mechanisms in centronuclear and myotubular myopathies and latest treatment advances. Int J Mol Sci. 2021;22(21).
184	H Jungbluth, M Gautel. Pathogenic mechanisms in centronuclear myopathies. Front Aging Neurosci. 2014;6:339.
185	K Majczenko, AE Davidson, S Camelo-Piragua, et al. Dominant mutation of CCDC78 in a unique congenital myopathy with prominent internal nuclei and atypical cores. Am J Hum Genet. 2012;91(2):365-371.
186	PB Agrawal, CR Pierson, M Joshi, et al. SPEG interacts with myotubularin, and its deficiency causes centronuclear myopathy with dilated cardiomyopathy. Am J Hum Genet. 2014;95(2):218-226.
187	I Vandersmissen, V Biancalana, L Servais, et al. An integrated modelling methodology for estimating the prevalence of centronuclear myopathy. Neuromuscul Disord. 2018;28(9):766-777.
188	J Laporte, LJ Hu, C Kretz, et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet. 1996;13(2):175-182.
189	F Blondeau, J Laporte, S Bodin, G Superti-Furga, B Payrastre, JL Mandel. Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway. Hum Mol Genet. 2000;9(15):2223-2229.
190	JO De Craene, DL Bertazzi, S B?r, FriantS Phosphoinositides. Major actors in membrane trafficking and lipid signaling pathways. Int J Mol Sci. 2017;18(3).
191	RJ Graham, F Muntoni, I Hughes, et al. Mortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis. Arch Dis Child. 2020;105(4):332-338.
192	MW Lawlor, JJ Dowling. X-linked myotubular myopathy. Neuromuscul Disord. 2021;31(10):1004-1012.
193	M Annoussamy, C Lilien, T Gidaro, et al. X-linked myotubular myopathy: a prospective international natural history study. Neurology. 2019;92(16):e1852-e1867.
194	V Biancalana, S Scheidecker, M Miguet, et al. Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues. Acta Neuropathol. 2017;134(6):889-904.
195	HL Tan, E Chan. Respiratory care in myotubular myopathy. ERJ Open Res. 2021;7(1).
196	N Maani, N Sabha, K Rezai, et al. Tamoxifen therapy in a murine model of myotubular myopathy. Nat Commun. 2018;9(1):4849.
197	PB Shieh, NL Kuntz, JJ Dowling, et al. Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial. Lancet Neurol. 2023;22(12):1125-1139.
198	JR Mendell, SA Al-Zaidy, LR Rodino-Klapac, et al. Current clinical applications of in vivo gene therapy with AAVs. Mol Ther. 2021;29(2):464-488.
199	N Salari, B Fatahi, E Valipour, et al. Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis. J Orthop Surg Res. 2022;17(1):96.
200	QQ Gao, EM McNally. The dystrophin complex: structure, function, and implications for therapy. Compr Physiol. 2015;5(3):1223-1239.
201	MA Waldrop, KM Flanigan. Update in Duchenne and Becker muscular dystrophy. Curr Opin Neurol. 2019;32(5):722-727.
202	Q Liao, Y Zhang, J He, K Huang. Global prevalence of myotonic dystrophy: an updated systematic review and meta-analysis. Neuroepidemiology. 2022;56(3):163-173.
203	LL Ozimski, M Sabater-Arcis, A Bargiela, R Artero. The hallmarks of myotonic dystrophy type 1 muscle dysfunction. Biol Rev Camb Philos Soc. 2021;96(2):716-730.
204	N Zernov, M Skoblov. Genotype-phenotype correlations in FSHD. BMC Med Genomics. 2019;12(2):43. Suppl.
205	F Zheng, L Qiu, L Chen, et al. Association of 4qA-specific distal D4Z4 hypomethylation with disease severity and progression in facioscapulohumeral muscular dystrophy. Neurology. 2023;101(3):e225-e237.
206	S Yamashita. Recent progress in oculopharyngeal muscular dystrophy. J Clin Med. 2021;10(7).
207	P Richard, C Trollet, T Stojkovic, et al. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy. Neurology. 2017;88(4):359-365.
208	HJ Kim, P Mohassel, S Donkervoort, et al. Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy. Nat Commun. 2022;13(1):2306.
209	NE Johnson, JM Statland. The Limb-Girdle muscular dystrophies. Continuum (Minneap Minn). 2022;28(6):1698-1714.
210	C Bouchard, JP Tremblay. Limb-Girdle muscular dystrophies classification and therapies. J Clin Med. 2023;12(14).
211	SA Heller, R Shih, R Kalra, PB Kang. Emery-Dreifuss muscular dystrophy. Muscle Nerve. 2020;61(4):436-448.
212	G Bonne, S Quijano-Roy. Emery-Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies. Handb Clin Neurol. 2013;113:1367-1376.