BoneKEy Reports | BoneKEy Watch
Deleting Mef2c in mice increases bone mass
DOI:10.1038/bonekey.2012.61
Investigation of the role of myocyte enhancer factors 2 (MEF2) in mice shows that Mef2c deficiency reduces expression of Sost, a known inhibitor of osteocyte bone formation. The Mef2c mutants had measurably increased bone mass in the axial and appendicular skeleton. Further studies using Sost-deficient mice showed similar increases in the mass of their long bones but not the axial skeleton, suggesting that the increase in bone mass was at least partly due to lowered Sost expression.
Cellular analysis showed that the parameters for bone formation were normal in Mef2c-deficient adult mice but that bone resorption had decreased significantly. Cortical expression of osteoprotegerin (OPG), the target gene for the Wnt/β-catenin pathway, and also Sfrp2 and Sfrp3, the Wnt signaling modulators, were strongly downregulated. The authors concluded that the Mef2c gene regulates cortical expression of the Sfrps and is also responsible for maintaining normal levels of Sost expression.
Editor's comment: These authors previously demonstrated that Sost downregulation by parathyroid hormone was mediated by repression of the MEF2C transcription factor, preventing its activation of a Sost enhancer. By deleting Mef2c specifically in osteocytes, they now demonstrate that this transcription factor actually regulates bone resorption in vivo via OPG and Sfrps. These results further emphasize the central role of osteocytes not only in regulating bone formation, but also in bone remodeling.
Subject terms: Transcription factors; bone remodeling; bone development
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