Effect of VCAM-1 on the Differentiation into Osteoclast

Abstract

In Orthodontic therapy, osteoclast precursors such as monocytes and macrophages migrate from vessels into the periodontium and then differentiate into osteoclasts, causing bone resorption. Focal adhesion kinase (FAK) is a 125-kDa non-receptor type tyrosine kinase that localizes to focal adhesions. FAK is involved in osteoclastic bone resorption. Vascular cell adhesion molecule-1 (VCAM -1) is bound to VLA-4(very late antigen-4) which is kind of the α₄ β1-integrin, and recruits monocytic osteoclast progenitors and elevates local osteoclast activity.In our present study we focused on VCAM-1 /α₄ integrin-mediated the differentiation into osteoclasts and found that this type of the differentiation was mediated through FAK. RAW267.4 expressed both α₄ integrins, and it was reported that expression of α₄ integrin and its counterreceptor, VCAM-1, was not enhanced in response to receptor activator of NF-B ligand (RANKL). Neutralizing antibodies against integrin α4 effectively inhibit the differentiation into osteoclasts and phosphorylation of FAK. These findings establish VCAM-1 regulate the differentiation into osteoclasts in bone.