Regulation of Wnt/β-catenin signaling within and from osteocytes.

Bone has long been known to be responsive to mechanical loading. For at least 25 years it has been known that osteocytes sense mechanical load, and because of their response to mechanical loading, osteocytes are believed to be the mechanosensory cell. The Wnt/β-catenin signaling pathway has been shown to be crucial in bone development. Mutations in LRP5 and SOST, which cause high bone mass, have increased interest in the Wnt pathway as a potential target for osteoporosis therapy and have helped link Wnt/β-catenin signaling to bone's response to mechanical loading. Because of its specificity to osteocytes, the Wnt inhibitor sclerostin is a target for anabolic bone therapies. The response of bone to mechanical loading is critically regulated by osteocytes secreting sclerostin, which binds to Lrp5.