Inhibition of ADAM10 in satellite cells accelerates muscle regeneration following muscle injury

Sakiko Mizuno, Masaki Yoda, Masayuki Shimoda, Kazuhiro Chiba, Masaya Nakamura, Keisuke Horiuchi

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Muscle injury is one of the most common orthopedic and sports disorders. For severe cases, surgical repair may be indicated; however, other than immobilization and the administration of anti-inflammatory drugs there is currently no effective conservative treatment for this condition. Satellite cells (SCs) are muscle-specific stem cells and are indispensable for muscle regeneration after muscle injury. SCs are activated upon muscle injury to proliferate and differentiate into myoblasts, which subsequently fuse into myofibers and regenerate the damaged muscle. We have previously shown that ADAM10, a membrane-anchored proteolytic enzyme, is essential for the maintenance of SC quiescence by activating the Notch signaling pathway in SCs. Because suppression of ADAM10 activity in SCs can activate SC differentiation, we asked whether inactivation of ADAM10 in SCs after muscle injury could enhance muscle regeneration. Using Adam10 conditional knockout mice, in which ADAM10 activity can specifically be suppressed in SCs, we found that partial inactivation of ADAM10 accelerates muscle regeneration after muscle injury. Nearly identical results were obtained by the administration of GI254023X, a selective ADAM10 inhibitor. The findings of the present study thus indicate that transient enhancement of SC differentiation after muscle injury expedites muscle regeneration and that ADAM10 can be a potential molecular target in treating muscle injuries.

本文言語English
ページ(範囲)2259-2265
ページ数7
ジャーナルJournal of Orthopaedic Research
36
8
DOI
出版ステータスPublished - 2018 8

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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