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Gorski et al. Exploring bone-muscle crosstalk by deleting Mbtps1 in osteocytes

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DOI:10.1038/bonekey.2016.44

Deletion of Mbtps1 in mice is embryonically lethal, so the authors used the late osteoblast/embedding osteocyte restricted DMP1 cre and the 3.6 Col1 cre constructs (expressed in long bones, skull, and tendons) to investigate the effect of a conditional, osteocyte-specific deletion of Mbtps1 protease in male mice.1

Adult mice with the deletion exhibited an age-related increase in contractile force (30%) and muscle mass (12%) in their slow twitch soleus muscle (SOL) but their bone mass, density, and other morphologies were indistinguishable from those of control mice. The only apparent difference was a 25% increase in bone stiffness.

To identify the candidate signaling pathways that mediate bone-muscle cross-talk, Gorski et al. then compared gene array data from mice with the osteocyte-specific deletion and from controls. They observed elevated expression of PAX7, MYOD1, MYOG, MYH3, NOTCH and an increased expression of gene pathways known to mediate EGFR signaling, circadian exercise, striated muscle contraction, glycolysis, fatty acid β-oxidation and adipogenesis.

Editor’s comment: Understanding the interactions between muscle and bone could lead to alternative ways of preventing and treating the bone and muscle loss that accompanies aging. It is interesting that the age-dependent effect on slow twitch muscle was more prominent in males, which might inform potential targeted treatments.

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