title: Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion.
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.
authors.affiliation: Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Somik
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Cardiovascular Medicine, Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei, China.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Yin
authors.affiliation: Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Deokhwa
authors.initials: D
authors.lastname: Nam
authors.affiliation: Department of Pediatric Surgery, Center for Stem Cell Research and Regenerative Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: kma@houstonmethodist.org.
authors.forename: Ke
authors.initials: K
authors.lastname: Ma
mesh_terms: D056930:ARNTL Transcription Factors / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D012333:RNA, Messenger
keywords: Circadian rhythm; Muscle regeneration; Proliferation; Satellite cell