Sost, independent of the non-coding enhancer ECR5, is required for bone mechanoadaptation.

ABSTRACT: Sclerostin (Sost) is a negative regulator of bone formation that acts upon the Wnt signaling pathway. Sost is mechanically regulated at both mRNA and protein level such that loading represses and unloading enhances Sost expression, in osteocytes and in circulation. The non-coding evolutionarily conserved enhancer ECR5 has been previously reported as a transcriptional regulatory element required for modulating Sost expression in osteocytes. Here we explored the mechanisms by which ECR5, or several other putative transcriptional enhancers regulate Sost expression, in response to mechanical stimulation. We found that in vivo ulna loading is equally osteoanabolic in wildtype and Sost^-/- mice, although Sost is required for proper distribution of load-induced bone formation to regions

SUBMITTER: Robling AG 

PROVIDER: S-EPMC6673653 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature