| First Author | Milanesi A | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 1 | Pages | 4-15 |
| PubMed ID | 26451739 | Mgi Jnum | J:232826 |
| Mgi Id | MGI:5780269 | Doi | 10.1210/en.2015-1443 |
| Citation | Milanesi A, et al. (2016) Thyroid Hormone Receptor alpha Plays an Essential Role in Male Skeletal Muscle Myoblast Proliferation, Differentiation, and Response to Injury. Endocrinology 157(1):4-15 |
| abstractText | Thyroid hormone plays an essential role in myogenesis, the process required for skeletal muscle development and repair, although the mechanisms have not been established. Skeletal muscle develops from the fusion of precursor myoblasts into myofibers. We have used the C2C12 skeletal muscle myoblast cell line, primary myoblasts, and mouse models of resistance to thyroid hormone (RTH) alpha and beta, to determine the role of thyroid hormone in the regulation of myoblast differentiation. T3, which activates thyroid hormone receptor (TR) alpha and beta, increased myoblast differentiation whereas GC1, a selective TRbeta agonist, was minimally effective. Genetic approaches confirmed that TRalpha plays an important role in normal myoblast proliferation and differentiation and acts through the Wnt/beta-catenin signaling pathway. Myoblasts with TRalpha knockdown, or derived from RTH-TRalpha PV (a frame-shift mutation) mice, displayed reduced proliferation and myogenic differentiation. Moreover, skeletal muscle from the TRalpha1PV mutant mouse had impaired in vivo regeneration after injury. RTH-TRbeta PV mutant mouse model skeletal muscle and derived primary myoblasts did not have altered proliferation, myogenic differentiation, or response to injury when compared with control. In conclusion, TRalpha plays an essential role in myoblast homeostasis and provides a potential therapeutic target to enhance skeletal muscle regeneration. |
