Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

Somik Chatterjee, Hongshan Yin, Deokhwa Nam, Yong Li, Ke Ma

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1-/- mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases.

Original languageEnglish (US)
Pages (from-to)200-210
Number of pages11
JournalExperimental Cell Research
Volume331
Issue number1
DOIs
StatePublished - Feb 1 2015

Keywords

  • Circadian rhythm
  • Muscle regeneration
  • Proliferation
  • Satellite cell

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion'. Together they form a unique fingerprint.

Cite this