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Thyroid Hormone Receptor α Plays an Essential Role in Male Skeletal Muscle Myoblast Proliferation, Differentiation, and Response to Injury.

Endocrinology | 2016

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) α and β, to determine the role of thyroid hormone in the regulation of myoblast differentiation. T3, which activates thyroid hormone receptor (TR) α and β, increased myoblast differentiation whereas GC1, a selective TRβ agonist, was minimally effective. Genetic approaches confirmed that TRα plays an important role in normal myoblast proliferation and differentiation and acts through the Wnt/β-catenin signaling pathway. Myoblasts with TRα knockdown, or derived from RTH-TRα PV (a frame-shift mutation) mice, displayed reduced proliferation and myogenic differentiation. Moreover, skeletal muscle from the TRα1PV mutant mouse had impaired in vivo regeneration after injury. RTH-TRβ 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, TRα plays an essential role in myoblast homeostasis and provides a potential therapeutic target to enhance skeletal muscle regeneration.

Pubmed ID: 26451739 RIS Download

Associated grants

  • Agency: NCATS NIH HHS, United States
    Id: UL1TR000124
  • Agency: NIDDK NIH HHS, United States
    Id: R01DK98576
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR000124
  • Agency: NIDDK NIH HHS, United States
    Id: K08 DK097295
  • Agency: BLRD VA, United States
    Id: I01 BX001966
  • Agency: NIDDK NIH HHS, United States
    Id: 1K08DK097295
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK098576

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