Role of Macrophages During Skeletal Muscle Regeneration and Hypertrophy-Implications for Immunomodulatory Strategies

Overview

Journal Physiol Rep

Specialty Physiology

Date 2022 Oct 6

PMID 36200266

Authors

Clara Bernard

Aliki Zavoriti

Quentin Pucelle

Benedicte Chazaud

Julien Gondin

Affiliations

Soon will be listed here.

Abstract

Skeletal muscle is a plastic tissue that regenerates ad integrum after injury and adapts to raise mechanical loading/contractile activity by increasing its mass and/or myofiber size, a phenomenon commonly refers to as skeletal muscle hypertrophy. Both muscle regeneration and hypertrophy rely on the interactions between muscle stem cells and their neighborhood, which include inflammatory cells, and particularly macrophages. This review first summarizes the role of macrophages in muscle regeneration in various animal models of injury and in response to exercise-induced muscle damage in humans. Then, the potential contribution of macrophages to skeletal muscle hypertrophy is discussed on the basis of both animal and human experiments. We also present a brief comparative analysis of the role of macrophages during muscle regeneration versus hypertrophy. Finally, we summarize the current knowledge on the impact of different immunomodulatory strategies, such as heat therapy, cooling, massage, nonsteroidal anti-inflammatory drugs and resolvins, on skeletal muscle regeneration and their potential impact on muscle hypertrophy.

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References

Hyldahl R, Peake J . Combining cooling or heating applications with exercise training to enhance performance and muscle adaptations. J Appl Physiol (1985). 2020; 129(2):353-365. DOI: 10.1152/japplphysiol.00322.2020. View

Serhan C . Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014; 510(7503):92-101. PMC: 4263681. DOI: 10.1038/nature13479. View

Baht G, Bareja A, Lee D, Rao R, Huang R, Huebner J . Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism. Nat Metab. 2020; 2(3):278-289. PMC: 7504545. DOI: 10.1038/s42255-020-0184-y. View

Warren G, Lowe D, Armstrong R . Measurement tools used in the study of eccentric contraction-induced injury. Sports Med. 1999; 27(1):43-59. DOI: 10.2165/00007256-199927010-00004. View

Saclier M, Lapi M, Bonfanti C, Rossi G, Antonini S, Messina G . The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration. Cells. 2020; 9(3). PMC: 7140652. DOI: 10.3390/cells9030708. View

Liao C, Lin L, Yu T, Hsu C, Pang J, Tsai W . Ibuprofen inhibited migration of skeletal muscle cells in association with downregulation of p130cas and CrkII expressions. Skelet Muscle. 2019; 9(1):23. PMC: 6714350. DOI: 10.1186/s13395-019-0208-z. View

Hatade T, Takeuchi K, Fujita N, Arakawa T, Miki A . Effect of heat stress soon after muscle injury on the expression of MyoD and myogenin during regeneration process. J Musculoskelet Neuronal Interact. 2014; 14(3):325-33. View

Lauritzen F, Paulsen G, Raastad T, Bergersen L, Owe S . Gross ultrastructural changes and necrotic fiber segments in elbow flexor muscles after maximal voluntary eccentric action in humans. J Appl Physiol (1985). 2009; 107(6):1923-34. DOI: 10.1152/japplphysiol.00148.2009. View

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

10.

Nielsen J, Aagaard P, Bech R, Nygaard T, Grondahl Hvid L, Wernbom M . Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood flow restriction. J Physiol. 2012; 590(17):4351-61. PMC: 3473290. DOI: 10.1113/jphysiol.2012.237008. View

11.

Child R, Brown S, Day S, Donnelly A, Roper H, Saxton J . Changes in indices of antioxidant status, lipid peroxidation and inflammation in human skeletal muscle after eccentric muscle actions. Clin Sci (Lond). 1998; 96(1):105-15. View

12.

Deng B, Wehling-Henricks M, Villalta S, Wang Y, Tidball J . IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. J Immunol. 2012; 189(7):3669-80. PMC: 3448810. DOI: 10.4049/jimmunol.1103180. View

13.

Nielsen J, Aagaard P, Prokhorova T, Nygaard T, Bech R, Suetta C . Blood flow restricted training leads to myocellular macrophage infiltration and upregulation of heat shock proteins, but no apparent muscle damage. J Physiol. 2017; 595(14):4857-4873. PMC: 5509865. DOI: 10.1113/JP273907. View

14.

Haas C, Butterfield T, Abshire S, Zhao Y, Zhang X, Jarjoura D . Massage timing affects postexercise muscle recovery and inflammation in a rabbit model. Med Sci Sports Exerc. 2013; 45(6):1105-12. PMC: 3632662. DOI: 10.1249/MSS.0b013e31827fdf18. View

15.

Dumont N, Wang Y, Rudnicki M . Intrinsic and extrinsic mechanisms regulating satellite cell function. Development. 2015; 142(9):1572-81. PMC: 4419274. DOI: 10.1242/dev.114223. View

16.

Kaneshige A, Kaji T, Zhang L, Saito H, Nakamura A, Kurosawa T . Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load. Cell Stem Cell. 2021; 29(2):265-280.e6. DOI: 10.1016/j.stem.2021.11.003. View

17.

Butterfield T, Zhao Y, Agarwal S, Haq F, Best T . Cyclic compressive loading facilitates recovery after eccentric exercise. Med Sci Sports Exerc. 2008; 40(7):1289-96. PMC: 4948996. DOI: 10.1249/MSS.0b013e31816c4e12. View

18.

Peake J, Roberts L, Figueiredo V, Egner I, Krog S, Aas S . The effects of cold water immersion and active recovery on inflammation and cell stress responses in human skeletal muscle after resistance exercise. J Physiol. 2016; 595(3):695-711. PMC: 5285720. DOI: 10.1113/JP272881. View

19.

Juban G, Chazaud B . Efferocytosis during Skeletal Muscle Regeneration. Cells. 2021; 10(12). PMC: 8699096. DOI: 10.3390/cells10123267. View

20.

Tscholl P, Vaso M, Weber A, Dvorak J . High prevalence of medication use in professional football tournaments including the World Cups between 2002 and 2014: a narrative review with a focus on NSAIDs. Br J Sports Med. 2015; 49(9):580-2. PMC: 4413681. DOI: 10.1136/bjsports-2015-094784. View