title: Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche.
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.
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Ohtani
authors.affiliation: Division for Therapies Against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Uezumi
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Mikami
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sato
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Hoshino
authors.affiliation: Division for Therapies Against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tsuchida
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miyagoe-Suzuki
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kazutake
authors.initials: K
authors.lastname: Tsujikawa
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: fukada@phs.osaka-u.ac.jp.
authors.forename: So-ichiro
authors.initials: S
authors.lastname: Fukada
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004917:Erythromycin / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D055153:Stem Cell Niche
chemical_list: D018003:Receptors, Calcitonin; D004917:Erythromycin; C057513:erythromycin propionate-N-acetylcysteinate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000111:Acetylcysteine