A disintegrin and metalloprotease 10 (ADAM10) is indispensable for maintenance of the muscle satellite cell pool

Sakiko Mizuno, Masaki Yoda, Masayuki Shimoda, Takahide Tohmonda, Yasunori Okada, Yoshiaki Toyama, Shin'Ichi Takeda, Masaya Nakamura, Morio Matsumoto, Keisuke Horiuchi

Research output: Contribution to journalArticle

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Abstract

Satellite cells (SCs) are muscle-specific stem cells that are essential for the regeneration of damaged muscles. Although SCs have a robust capacity to regenerate myofibers, the number of SCs decreases with aging, leading to insufficient recovery after muscle injury. We herein show that ADAM10 (a disintegrin and metalloprotease 10), a membrane-bound proteolytic enzyme with a critical role in Notch processing (S2 cleavage), is essential for the maintenance of SC quiescence. We generated mutant mice in which ADAM10 in SCs can be conditionally abrogated by tamoxifen injection. Tamoxifen-treated mutant mice did not show any apparent defects and grew normally under unchallenged conditions. However, these mice showed a nearly complete loss of muscle regeneration after chemically induced muscle injury. In situ hybridization and flow cytometric analyses revealed that the mutant mice had significantly less SCs compared with wild type controls. Of note, we found that inactivation ofADAM10in SCs severely compromised Notch signaling and led to dysregulated myogenic differentiation, ultimately resulting in deprivation of the SC pool in vivo. Taken together, the present findings underscore the role ofADAM10as an indispensable component of Notch signaling in SCs and for maintaining the SC pool.

Original languageEnglish
Pages (from-to)28456-28464
Number of pages9
JournalJournal of Biological Chemistry
Volume290
Issue number47
DOIs
Publication statusPublished - 2015 Nov 20

Fingerprint

Disintegrins
Metalloproteases
Muscle Cells
Muscle
Maintenance
Satellites
Muscles
Tamoxifen
Regeneration
Wounds and Injuries
In Situ Hybridization
Stem cells
Peptide Hydrolases
Stem Cells
Cell Count
Aging of materials
Injections
Membranes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

A disintegrin and metalloprotease 10 (ADAM10) is indispensable for maintenance of the muscle satellite cell pool. / Mizuno, Sakiko; Yoda, Masaki; Shimoda, Masayuki; Tohmonda, Takahide; Okada, Yasunori; Toyama, Yoshiaki; Takeda, Shin'Ichi; Nakamura, Masaya; Matsumoto, Morio; Horiuchi, Keisuke.

In: Journal of Biological Chemistry, Vol. 290, No. 47, 20.11.2015, p. 28456-28464.

Research output: Contribution to journalArticle

Mizuno, Sakiko ; Yoda, Masaki ; Shimoda, Masayuki ; Tohmonda, Takahide ; Okada, Yasunori ; Toyama, Yoshiaki ; Takeda, Shin'Ichi ; Nakamura, Masaya ; Matsumoto, Morio ; Horiuchi, Keisuke. / A disintegrin and metalloprotease 10 (ADAM10) is indispensable for maintenance of the muscle satellite cell pool. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 47. pp. 28456-28464.
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