Abstract
We evaluated the effects of hypo- and hyperthyroid statuses during the initial phase of skeletal muscle regeneration in rats. To induce hypo- or hyperthyroidism, adult male Wistar rats were treated with methimazole (0.03 %) or T4 (10 μg/100 g), respectively, for 10 days. Three days before sacrifice, a crush injury was produced in the solear muscles of one half of the animals, while the other half remained intact. T3, T4, TSH, and leptin serum levels were not affected by the injury. Serum T3 and T4 levels were significantly increased in hyperthyroid and hyper-injury animals. Hypothyroidism was confirmed by the significant increase in serum TSH levels in hypothyroid and hypo-injury animals. Injury increased cell infiltration and macrophage accumulation especially in hyperthyroid animals. Both type 2 and type 3 deiodinases were induced by lesion, and the opposite occurred with the type 1 isoform, at least in the control and hyperthyroid groups. Injury increased both MyoD and myogenin expression in all the studied groups, but only MyoD expression was increased by thyroidal status only at the protein level. We conclude that thyroid hormones modulate skeletal muscle regeneration possibly by regulating the inflammatory process, as well as MyoD and myogenin expression in the injured tissue.
Similar content being viewed by others
References
C.E. Stewart, J. Rittweger, Adaptive processes in skeletal muscle: molecular regulators and genetic influences. J. Musculoskelet. Neuronal Interact. 6(1), 73–86 (2006)
P.S. Zammit, J.R. Beauchamp, The skeletal muscle satellite cell: stem cell or son of stem cell? Differentiation 68, 193–204 (2001)
J.G. Tidball, Inflammatory processes in muscle injury and repair. Am J Physiol. Regul. Integr. Comp. Physiol. 288, R345–R353 (2005)
S. Brunelli, P. Rovere-Querini, The immune system and the repair of skeletal muscle. Pharmacol. Res. 5, 117–121 (2008)
M.I. Massimimo, E. Rapizzi, M. Cantini, L.D. Libera, F. Mazzoleni, P. Arslan, U. Carraro, ED2+ macrophages increase selectively myoblast proliferation in muscle cultures. Biochem. Biophys. Res. Commun. 235(3), 754–759 (1997)
T.A. Robertson, M.A. Maley, M.D. Grounels, J.M. Papadimitriou, The role of macrophages in skeletal muscle regeneration with particular reference to chemotaxis. Exp. Cell Res. 207, 321–331 (1993)
L.A. Di Pietro, Wound healing: the role of the macrophage and other immune cells. Shock 4, 233–240 (1995)
M. Summan, G.L. Warren, R.R. Mercer, R. Chapman, T. Hulderman, N. Van Rooijen, P.P. Simeonova, Macrophages and skeletal muscle regeneration: a clodronate-containing liposome depletion study. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R1488–R1495 (2006)
J.M. Peterson, F.X. Pizza, Cytokines derived from cultured skeletal muscle cells after mechanical strain promote neutrophil chemotaxis in vitro. J. Appl. Physiol. 106, 130–137 (2009)
T. Soukup, I. Jirmanová, Regulation of myosin expression in developing regeneratin extrafusal and intrafusal muscle fibers with special emphasis on the role of thyroid hormones. Physiol. Res. 49, 617–633 (2000)
S. D’Arezzo, S. Incerpi, F.B. Davis, F. Accontia, M. Marino, R.N. Farias, P.J. Davis, Rapid nongenomic effects of 3,5,3′-triiodo-l-thronine on the intracellular pH of L-6 myoblasts are mediated by intracellular calcium mobilization and kinase pathways. Endocrinology 145(12), 5694–5703 (2004)
B.H. Penn, C.A. Berker, D.A. Bergustrom, J. Tapscott, How to MEK muscle. Mol. Cell 8(2), 245–246 (2001)
R.L. Perry, M.H. Parker, M.A. Rudnicki, Activated MEK-1 binds to nuclear Myo D transcriptional complex to repress transactivation. Mol. Cell 8(2), 291–301 (2001)
D.G. Moreira, M.P. Marassi, V.M. Corrêa da Costa, D.P. Carvalho, D. Rosenthal, Effects of ageing and pharmacological hypothyroidism on pituitary–thyroidal axis of Dutch–Miranda and Wistar rats. Exp. Gerontol. 40, 330–334 (2005)
A.L.R.C. Leal, T.U. Pantaleão, D.G. Moreira, M.P. Marassi, V.S. Pereira, D. Rosenthal, V.M. Corrêa da Costa, Hypothyroidism and hyperthyroidism modulates Ras–MAPK intracellular pathway in murine thyroids. Endocrine 31(2), 174–178 (2007)
T.U. Pantaleão, F. Mousovich, D. Rosenthal, D.P. Carvalho, V.M. Corrêa da Costa, Effect of serum estradiol and leptin levels on thyroid function, food intake and body weight gain in female Wistar rats. Steroids 75, 638–642 (2010)
M.M. Bradford, A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein dye binding. Anal. Biochem. 72, 248–254 (1976)
K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2−∆∆CT method. Methods 25, 402–408 (2001)
G.L. Warren, T. Hulderman, D. Mishra, X. Gao, L. Millecchia, L. O’Farrell, W.A. Kuziel, P.P. Simeonova, Chemokine receptor CCR2 involvement in skeletal muscle regeneration. FASEB J 19, 413–415 (2001)
B.K. Pedersen, M.A. Febbraio, Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol. Rev. 88, 1379–1406 (2008)
A. Marsili, D. Tang, J.W. Harney, P. Singh, A.M. Zavacki, M. Dentice, D. Salvatore, P.R. Larsen, Type II iodothyronine deiodinase provides intracellular 3, 5, 3′-triiodothyronine to normal and regenerating mouse skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 301, E818–E824 (2011)
M. Dentice, A. Marsili, R. Ambrosio, O. Guardiola, A. Sibilio, J. Paik, G. Minchiotti, R.A. DePinho, G. Fenzi, P.R. Larsen, D. Salvatore, The FoxO3/type 2 deiodinase pathway is required for normal mouse myogenesis and muscle regeneration. J. Clin. Investig. 120, 4021–4030 (2012)
R. Ambrosio, V. Damiano, A. Sibilio, M.A. De Stefano, V.E. Avvedimento, D. Salvatore, M. Dentice, Epigenetic control of type 2 and 3 deiodinases in myogenesis: role of Lysine-specific Demethylase enzyme and FoxO3. Nucleic Acids Res. 41(6), 3551–3562 (2013)
D. Salvatore, W.S. Simonides, M. Dentice, A.M. Zavacki, P.R. Larsen, Thyroid hormones and skeletal muscle—new insights and potential implications. Nat. Rev. (2013). doi:10.1038/nrendo.2013.238
M.P. Rozing, R.G.J. Westendorp, A.B. Maier, C.A. Wijsman, M. Frölich, A.J.M. de Craen, D. van Heemst, Serum triiodothyronine levels and inflammatory cytokine production capacity. Age 34, 195–201 (2012)
K. Yeow, C. Cabane, L. Turchi, G. Ponzio, B. Dérijard, Increased MAPK signaling during in vitro muscle wounding. Biochem. Biophys. Res. Commun. 293, 112–119 (2002)
M. Murgia, A.L. Serrano, E. Calábria, G. Pallafacchina, T. Lomo, S. Schiaffino, Ras is involved in nerve-activity-dependent regulation of muscle genes. Nat. Cell Biol. 2, 142–147 (2000)
A. Rinnov, C. Yfanti, S. Nielsen, T.C.A. Akerstrom, L. Peijs, A. Zankari, C.P. Fischer, B.K. Pedersen, Endurance training enhances skeletal muscle interleukin-15 in human male subjects. Endocrine 45, 271–278 (2014)
L. Ceglia, D.A. Rivas, R.M. Pojednic, L.L. Price, S.S. Harris, D. Smith, R.A. Fielding, B.D. Hughes, Effects of alkali supplementation and vitamin D insufficiency on rat skeletal muscle. Endocrine 44, 454–464 (2013)
S.C. Forbes, J.P. Little, D.G. Candow, Exercise and nutritional interventions for improving aging muscle health. Endocrine 42, 29–38 (2012)
D.T. Thomas, Could vitamin D and bicarbonate supplementation synergize to mitigate age-related loss of muscle? Endocrine 44, 280–282 (2013)
L. Cianferotti, M.L. Brandi, Muscle-bone interactions: basic and clinical aspects. Endocrine 45, 165–177 (2014)
Acknowledgments
The authors gratefully acknowledge the technical assistance of Advaldo Nunes Bezerra, José Humberto Tavares de Abreu, Norma Lima de Araújo Faria, and Wagner Nunes Bezerra. This work was supported by the grants from Fundação Carlos Chagas Filho de Amparo `a Pesquisa do Estado do Rio de Janeiro (FAPERJ), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Conflict of interest
Authors declare no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Leal, A.L.R.C., Albuquerque, J.P.C., Matos, M.S. et al. Thyroid hormones regulate skeletal muscle regeneration after acute injury. Endocrine 48, 233–240 (2015). https://doi.org/10.1007/s12020-014-0271-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-014-0271-5