Bone Abstracts

Tyrosine kinase c-Src plays an important role in actin ring formation and bone resorption activity in osteoclasts. Therefore, c-Src has been targeted for the treatment of osteolytic disorders. In the present study, we investigated anti-resorptive effect of dibenzazepine (DBZ), one of the γ-secretase inhibitors (GSIs), on osteoclast-mediated excessive bone resorption. DBZ did not affect osteoclast differentiation, but disturbed actin ring formation and inhibited osteoclast-induced bone resorption by suppressing c-Src kinase activity. In addition, the localization of c-Src exhibited scattered distribution throughout the cytoplasm by DBZ treatment. Consistent with the in vitro results, osteoclastic bone resorption was strongly reduced by administration of DBZ in IL-1 induced bone loss model. Collectively, we demonstrated that DBZ had a potent inhibitory activity on bone resorptive activity by Src activity in mature osteoclasts. Our results suggest that DBZ may serve as a useful agent for osteoclast-mediated excessive bone resorption.