Regulation of osteoclast polarization.

Osteoclast function consists of several processes: recognition of mineralized tissues, development of ruffled borders and sealing zones, secretion of acids and proteolytic enzymes into the space beneath the ruffled border, and incorporation and secretion of bone degradation products using the transcytosis system. One of the most important questions concerning osteoclast function is how osteoclasts recognize bone and polarize. During the past decade, new approaches have been taken to investigate the regulation of osteoclast polarization. Attachment of osteoclasts to some proteins containing the Arg-Gly-Asp sequence motif through vitronectin receptors is the first step in inducing the polarization of osteoclasts. Physical properties of bone such as hardness or roughness are also required to induce osteoclast polarity. Osteoclasts cultured even on plastic dishes secrete protons toward the dish surface, suggesting that osteoclasts recognize plastic as a mineralized matrix and secrete protons. This notion was supported by the recent findings that bisphosphonates and reveromycin A were specifically incorporated into polarized osteoclasts cultured even on plastic dishes. On the other hand, a sealing zone, defined as a thick band of actin, is induced in osteoclasts adherent only on an apatite-containing mineralized matrix. These results suggest that osteoclasts recognize physical properties of the mineralized tissue to secrete protons, and also sense apatite itself or components of apatite to form the sealing zone. Here, we review recent findings on the regulation of osteoclast polarization. We also discuss how osteoclasts recognize mineralized tissues to form the sealing zone.