Thyroid Hormone Receptor α is Essential to Maintain the Satellite Cell Niche during Skeletal Muscle Injury and Sarcopenia of Aging.

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Thyroid Hormone Receptor α is Essential to Maintain the Satellite Cell Niche during Skeletal Muscle Injury and Sarcopenia of Aging.

Thyroid. 2017 Aug 28;:

Authors: Milanesi A, Lee JW, Yang A, Liu YY, Sedrakyan S, Cheng SY, Perin L, Brent GA

Abstract
BACKGROUND: Myopathic changes are commonly described in hypothyroid and hyperthyroid patients, including muscular atrophy and weakness. Satellite cells (SCs) play a major role in skeletal muscle maintenance and regeneration after injury. A mouse model of Resistance to Thyroid Hormone (RTH)-TRα1PV demonstrated impaired skeletal muscle regeneration after injury with significant reduction of SCs, suggesting that exhaustion of the SC pool contributes to the impaired regeneration. To test this hypothesis, we analyzed SC activation and proliferation in vivo in response to skeletal muscle injury and during aging.
METHODS: We analyzed SCs of TRα1PV male mice 4 days after cardiotoxin-induced muscle injury and compared with wild type (WT) male animals. We injected TRα-knockdown C2C12 myoblasts into injured skeletal muscle and compared the in vivo behavior, 4 days after transplantation, with control C2C12 myoblasts. We compared skeletal muscle regeneration in younger and older TRα1PV and WT animals.
RESULTS: The total number of SCs in skeletal muscle of TRα1PV mice was significantly lower than control, both before and shortly after muscle injury, with significant impairment of SC activation, consistent with SC pool exhaustion. TRα-knockdown myoblasts showed impaired in vivo proliferation and migration. TRα1PV mice had skeletal muscle loss and significant impairment in skeletal muscle regeneration with aging. This translated to a significant reduction of the SC pool with aging, compared with wild type mice.
CONCLUSION: TRα plays an important role in maintenance of the SC pool. Impaired skeletal muscle regeneration in TRα1PV mice is associated with insufficient SC activation and proliferation, as well as the progressive loss of the satellite cell pool with aging. Regulation of the SC pool and SC proliferation provides a therapeutic target to enhance skeletal muscle regeneration and possible slow age-associated sarcopenia.

PMID: 28847239 [PubMed - as supplied by publisher]

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