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Vol. 95, Issue 7, 3597-3602, March 31, 1998
* Research Institute of Life Science, Snow Brand Milk Products Co.,
Ltd., 519 Ishibashi-machi, Shimotsuga-gun, Tochigi 329-0512, Japan; and
§ Department of Biochemistry, School of Dentistry, Showa
University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Communicated by Hector F. DeLuca, University of Wisconsin, Madison,
WI, January 22, 1998 (received for review December 15, 1997)
Osteoclasts, the multinucleated cells that resorb bone, develop
from hematopoietic cells of monocyte/macrophage lineage.
Osteoclast-like cells (OCLs) are formed by coculturing spleen cells
with osteoblasts or bone marrow stromal cells in the presence of
bone-resorbing factors. The cell-to-cell interaction between
osteoblasts/stromal cells and osteoclast progenitors is essential for
OCL formation. Recently, we purified and molecularly cloned
osteoclastogenesis-inhibitory factor (OCIF), which was identical to
osteoprotegerin (OPG). OPG/OCIF is a secreted member of the tumor
necrosis factor receptor family and inhibits osteoclastogenesis by
interrupting the cell-to-cell interaction. Here we report the
expression cloning of a ligand for OPG/OCIF from a complementary DNA
library of mouse stromal cells. The protein was found to be a member of
the membrane-associated tumor necrosis factor ligand family and induced
OCL formation from osteoclast progenitors. A genetically engineered
soluble form containing the extracellular domain of the protein induced OCL formation from spleen cells in the absence of osteoblasts/stromal cells. OPG/OCIF abolished the OCL formation induced by the protein. Expression of its gene in osteoblasts/stromal cells was up-regulated by bone-resorbing factors. We conclude that the membrane-bound protein
is osteoclast differentiation factor (ODF), a long-sought ligand
mediating an essential signal to osteoclast progenitors for their
differentiation into osteoclasts. ODF was found to be identical to
TRANCE/RANKL, which enhances T-cell growth and dendritic-cell function. ODF seems to be an important regulator in not only
osteoclastogenesis but also immune system.
Copyright © 1998 by The National Academy of Sciences 0027-8424/98/953597-6$2.00/0
Cell Biology
Osteoclast differentiation factor is a ligand for
osteoprotegerin/osteoclastogenesis-inhibitory factor and is
identical to TRANCE/RANKL
,,,
,
These authors contributed equally to this work.
To whom reprint requests should be addressed. e-mail:
fvbd7042{at}mb.infoweb.or.jp.
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