Regulatory mechanisms of RANKL presentation to osteoclast precursors.
It is important to understand the molecular mechanisms regulating osteoclast formation, as excess activation of osteoclasts is associated with various osteopenic disorders. Receptor activator of nuclear factor kappa B (RANKL) is a central player in osteoclastogenesis. Recent findings suggest that osteocytes are the major supplier of RANKL to osteoclast precursors. It has also been suggested that osteocyte cell death upregulates the RANKL/osteoprotegerin (OPG) ratio in viable osteocytes adjacent to apoptotic osteocytes in areas of bone microdamage, thus, contributing to localized osteoclast formation. Indeed, viable osteocytes can provide RANKL through direct interactions with osteoclast precursors at osteocyte dendritic processes. In addition, OPG tightly regulates RANKL cell surface presentation in osteocytes, which contributes to the inhibition of RANKL signaling, as well as the decoy receptor function of OPG. By contrast, the physiological role of RANKL in osteoblasts is yet to be clarified, although similar mechanisms of regulation are observed in both osteocytes and osteoblasts.
Department of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan, mhonma-tky@umin.ac.jp.
Masashi
M
Honma
Yuki
Y
Ikebuchi
Yoshiaki
Y
Kariya
Hiroshi
H
Suzuki
D016723:Bone Remodeling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology*; D010011:Osteocytes / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism* / Q000502:physiology; D053245:RANK Ligand / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D053244:Osteoprotegerin; D053245:RANK Ligand