Regulatory mechanisms of sclerostin expression during bone remodeling.

Osteocytes are embedded in bone matrices and are connected to each other to respond to mechanical loading on bone. Recent studies have demonstrated the roles of mechanical loading in bone accrual. Bone responds to mechanical loading by decreasing the expression of sclerostin, an inhibitor of Wnt/β-catenin signals, in osteocytes. This increases bone mass because the activation of Wnt/β-catenin signals in bone microenvironments promotes bone formation and suppresses bone resorption. Thus, in recent years, sclerostin have attracted increasing attention in bone metabolism. However, the regulatory mechanism of sclerostin expression during bone remodeling has not been fully elucidated. In this review, we summarized the regulation of bone formation and resorption by Wnt signals, a Wnt/β-catenin signal inhibitor sclerostin, and molecular mechanisms by which the expression of sclerostin is suppressed by mechanical loading and parathyroid hormone. We also discuss a possibility that osteoclasts suppress the expression of sclerostin during bone remodeling, which in turn, promote bone formation. The effectiveness of an anti-sclerostin antibody with anti-dickkopf-1 antibody for increasing bone mass was discussed.