BoneKEy Reports | BoneKEy Watch

Sost, ECR5, Mef2C and van Buchem disease


Patients with genetic abnormalities that prevent them expressing sclerostin develop either sclerosteosis or van Buchem (VB) disease. Both result in excessive Wnt signaling, which disrupts bone homeostasis. VB patients are homozygous for a coding deletion that renders them incapable of activating the SOST gene in bone.

Collette et al. investigated the relationship between ECR5, a potential bone enhancer located in the region deleted in VB, and the transcription factor Mef2C, which controls it in vitro. They first confirmed that ECR5 acts in vivo as a tissue-specific bone enhancer in neonatal and adult mice. Mef2C was indeed necessary for Sost expression in osteocytes, as mediated by ECR5.

Overall, the results showed that Mef2C is necessary for the transcriptional activation of Sost in osteocytes, and is therefore an upstream regulator of Wnt signaling. Furthermore, Sost is a transcriptional target for Mef2C in bone; further studies of these interactions are now necessary to explore how Sost and the Wnt pathway can be targeted.

Editor's comment: This study provides important evidence that Sost gene transcription is enhanced by Mef2C, a transcription factor that interacts with the ECR5 enhancer that is located distal to the Sost coding region, within the stretch of DNA that is deleted in van Buchem disease. This observation will aid our understanding of the mechanism by which transcriptional regulation of Sost occurs, and may result in the development of a new anabolic therapy.

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