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Bone Abstracts (2014) 3 PP170 | DOI: 10.1530/boneabs.3.PP170

Cell biology: osteoclasts and bone resorption

DBZ, a γ-secretase inhibitor, suppresses bone resorption by inhibiting c-Src activity

Won Jong Jin, Ha-Neui Kim, Hong-Hee Kim & Zang Hee Lee

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Department of Cell and Developmental Biology, Seoul National University School of Dentistry, Seoul, Republic of Korea.


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.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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