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Schroder et al. Disrupting the molecular clock in muscle also affects bone



DOI:10.1038/bonekey.2016.33

Circadian rhythms in mice are maintained by a molecular clock controlled by a transcription/translation feedback loop in which the gene Bmal1 codes for a core transcription factor. In this study, mice were bred with an inducible deletion of Bmal1 in their skeletal muscle to allow investigation of the phenotypic changes that occurred when the gene was knocked out, disrupting the skeletal muscle molecular clock.

Mice in which Bmal1 was inducibly and specifically deleted in muscle showed a very similar phenotype to mice bred with a germline Bmal1 knockout—they showed increased muscle fibrosis, an increase in percentage of oxidative muscle fibers and a reduction in specific muscle tension.

Although the deletion only occurred in muscle in the mice in this study, the effects went far beyond muscle tissue. Significant alterations were also noted in bone and cartilage throughout the bodies of the mice, with increased calcification of bone and a decrease of collagen within joints observed. These changes, combined with the functional muscle changes resulted in a substantially altered gait.

Editor’s comment: This study uncovers a fundamental role for the skeletal muscle ‘clock’ in maintaining homeostasis within the musculoskeletal system, with interesting potential implications for ageing. It also identifies a transcription factor with a role in crosstalk between skeletal muscle, cartilage and bones.


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