Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Division for Therapies Against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
Cell Rep. 2015 Oct 13;13(2):302-14. doi: 10.1016/j.celrep.2015.08.083. Epub 2015 Oct 1.
Calcitonin receptor (Calcr) is expressed in adult muscle stem cells (muscle satellite cells [MuSCs]). To elucidate the role of Calcr, we conditionally depleted Calcr from adult MuSCs and found that impaired regeneration after muscle injury correlated with the decreased number of MuSCs in Calcr-conditional knockout (cKO) mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA pathway but had no impact on myogenic differentiation of MuSCs in an undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found outside their niche in Calcr-cKO mice, demonstrating cell relocation. This emergence from the sublaminar niche was prevented by the Calcr-cAMP-PKA and Calcr-cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state and in their location, maintaining the MuSC pool.
降钙素受体（Calcr）在成年肌肉干细胞（肌肉卫星细胞[MuSCs]）中表达。为了阐明 Calcr 的作用，我们条件性地从成年 MuSCs 中耗尽 Calcr，发现肌肉损伤后的再生受损与 Calcr 条件性敲除（cKO）小鼠中 MuSCs 数量减少有关。Calcr 信号通过 cAMP-PKA 途径维持 MuSC 休眠，但对未分化状态下 MuSCs 的成肌分化没有影响。Calcr-cKO 小鼠中异常的静止状态导致 MuSC 通过细胞凋亡减少。此外，在 Calcr-cKO 小鼠中发现 MuSCs 位于其龛位之外，表明细胞发生了重定位。Calcr-cAMP-PKA 和 Calcr-cAMP-Epac 途径下游的 Calcr 阻止了这种从亚层龛位的出现。总之，这些发现表明，Calcr 通过使 MuSCs 保持静止状态并保持其位置来发挥其作用，从而维持 MuSC 池。
