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J Biol Chem, Vol. 275, Issue 7, 4858-4864, February 18, 2000
From the Osteoclast progenitors differentiate into mature
osteoclasts in the presence of receptor activator of NF-
Tumor Necrosis Factor-
Induces Differentiation of and Bone
Resorption by Osteoclasts*
, Teijin Institute for Biomedical Research,
Teijin Limited, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, and the
§ Department of Life Science, Tokyo Institute of Technology,
4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan
B (RANK)
ligand on stromal or osteoblastic cells and monocyte macrophage
colony-stimulating factor (M-CSF). The soluble RANK ligand induces the
same differentiation in vitro without stromal cells. Tumor
necrosis factor-
(TNF-), a potent cytokine involved in the
regulation of osteoclast activity, promotes bone resorption via a
primary effect on osteoblasts; however, it remains unclear whether
TNF- can also directly induce the differentiation of osteoclast
progenitors into mature osteoclasts. This study revealed that TNF-
directly induced the formation of tartrate-resistant acid phosphatase
(TRAP)-positive multinucleated cells (MNCs), which produced resorption
pits on bone in vitro in the presence of M-CSF. The bone
resorption activity of TNF--induced MNCs was lower than that of
soluble RANK ligand-induced MNCs; however, interleukin-1
stimulated
this activity of TNF--induced MNCs without an increase in the number
of MNCs. In this case, interleukin-1 did not induce TRAP-positive
MNC formation. The osteoclast progenitors expressed TNF receptors, p55
and p75; and the induction of TRAP-positive MNCs by TNF- was
inhibited completely by an anti-p55 antibody and partially by an
anti-p75 antibody. Our findings presented here are the first to
indicate that TNF- is a crucial differentiation factor for
osteoclasts. Our results suggest that TNF- and M-CSF play an
important role in local osteolysis in chronic inflammatory diseases.
*
This work was supported in part by a grant-in-aid for
scientific research from the Ministry of Education, Science, and
Culture of Japan.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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