Inhibition of osteoclast actin ring formation and activation by phloretin through disturbing integrin αvβ3‐PYK2 pathway (1045.29)

Abstract

Osteoclast activation is important for bone remodeling and is altered in multiple bone disorders such as osteoporosis. This process requires cell adhesion and extensive actin cytoskeletal reorganization. Phloretin, a dihydrochalcone and a type of natural phenols, can be found in apple tree leaves. The goal of this study was to define the process and mechanism of bone resorption. RAW 264.7 macrophages were incubated with 1‐20 μM phloretin for 5 days in the presence of RANKL. RANKL stimulated Akt activation and c‐Src expression, which was blunted by phloretin. The integrin αvβ3, heterodimer of adhesion receptors, is crucial in osteoclast activation mediating cell‐matrix and cell‐cell interactions. Phloretin suppressed integrin β3 induction and PYK2 activation elevated by RANKL, indicating its inhibition of osteoclastic fusion. The activation of PYK2, a major cell adhesion‐activated tyrosine kinase in osteoclasts, is required for the formation of actin rings. Taken together, these results suggest that phloretin was an inhibitor of actin ring formation, disrupting integrin‐PYK2 pathway for the regulation of actin cytoskeletal organization in osteoclasts.Grant Funding Source: Supported by Brain Korea 21 plus