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Osteocytes are the central target for bone anabolism via Wnt signaling
Tu et al. report enhanced bone anabolism in dominant active (da)ßcatOt mice, in which canonical Wnt signaling is activated exclusively in osteocytes.
The daßcatOt mice generated in the study developed normally but showed increased bone mineral density (BMD) throughout their skeleton. They showed higher bone volume in their cortical and cancellous/trabecular compartments compared to controls. Bone matrix production and periosteal bone formation rate were also higher and the daßcatOt mice had a high number of osteoblasts and osteoclasts in both their cortical and cancellous bone.
Anti-osteoclastogenic and pro-osteoclastogenic cytokines were also elevated, as were Wnt and Notch signaling genes and osteocyte and osteoblast markers. The Notch pathway was also activated in a Sost-sclerostin dependent manner.
In contrast, mice expressing the same signaling pathway exclusively in osteoblasts died shortly after birth due to leukemia and showed decreased bone resorption.
Editor’s comment: Surprising findings of a coupled increase in bone formation and resorption when beta-catenin signaling is constitutively activated in osteocytes. Indeed previous work of osteocyte specific deletion of beta-catenin using the same promoter (Dmp1) had shown an increase in bone resorption and low bone mass without changes in bone formation. The most unexplained finding in this study is an increase of periosteal bone formation concomitant to an increase of Sost expression in mice with activated osteocytes-beta catenin.
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