Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche

Masahiko Yamaguchi, Yoko Watanabe, Takuji Ohtani, Akiyoshi Uezumi, Norihisa Mikami, Miki Nakamura, Takahiko Sato, Masahito Ikawa, Mikio Hoshino, Kunihiro Tsuchida, Yuko Miyagoe-Suzuki, Kazutake Tsujikawa, Shin'ichi Takeda, Hiroshi Yamamoto, So ichiro Fukada

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)302-314
Number of pages13
JournalCell Reports
Volume13
Issue number2
DOIs
Publication statusPublished - 13-10-2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Yamaguchi, M., Watanabe, Y., Ohtani, T., Uezumi, A., Mikami, N., Nakamura, M., Sato, T., Ikawa, M., Hoshino, M., Tsuchida, K., Miyagoe-Suzuki, Y., Tsujikawa, K., Takeda, S., Yamamoto, H., & Fukada, S. I. (2015). Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche. Cell Reports, 13(2), 302-314. https://doi.org/10.1016/j.celrep.2015.08.083