Calcitonin receptor downregulation and exercise-conditioned blood enable systemic muscle stem cell proliferation.

ABSTRACT: Quiescent muscle stem cells (MuSCs) respond to exercise; however, the coordinated regulation of increased loading, exerkines, and quiescence signaling remains unclear. We found that increased loading reduces calcitonin receptor (CalcR) expression, and forced activation of protein kinase A (PKA), a downstream of CalcR signaling, suppresses MuSC proliferation. Although MuSC-specific Calcr knockout (C-cKO) alone is insufficient, exercised C-cKO mice exhibit significant MuSC proliferation independent of increased loading. Reinforcement of CalcR signaling, either through PKA induction or Yap1 depletion, suppresses MuSC proliferation. Load-independent MuSC proliferation is also suppressed by the deletion of gp130 in C-cKO mice. Serum from exercised mice recapitulates MuSC proliferation in all an

SUBMITTER: Zhang L 

PROVIDER: S-EPMC12658206 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature