N. Nakagawa et al., RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis, BIOC BIOP R, 253(2), 1998, pp. 395-400
Citations number
33
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Osteoclast differentiation factor (ODF) is a ligand for osteoclastogenesis-
inhibitory factor/osteoprotegerin (OCIF/OPG), and mediates an essential sig
nal for osteoclastogenesis. Soluble-form ODF binds directly to osteoclast p
rogenitors, suggesting the presence of a membrane-bound receptor for ODF (O
DFR) on the cells. To understand the ODF-mediated signal transduction mecha
nism in osteoclastogenesis, we molecularly cloned ODFR from a mouse macroph
age-like osteoclast progenitor cell line, C7. Nucleotide sequence analysis
revealed that ODFR is identical to RANK, a recently identified member of th
e tumor necrosis factor receptor (TNFR) family, which is involved in the re
gulation of dendritic cell function, A polyclonal antibody against the extr
acellular domain of RANK induced osteoclastogenesis in the presence of macr
ophage colony-stimulating factor (M-CSF). In contrast; both a genetically e
ngineered soluble RANK and Fab fragment of the antibody blocked the binding
of ODF to RANK and ODF-mediated osteoclastogenesis. These results indicate
that RANK is the signaling receptor essential for ODF-mediated osteoclasto
genesis. (C) 1998 Academic Press.