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*
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan; and
Department of Oral Science, National Institute of Infectious Diseases, Tokyo, Japan
Osteoclast differentiation factor (ODF), a novel member of the TNF
ligand family, is expressed as a membrane-associated protein by
osteoblasts/stromal cells. The soluble form of ODF (sODF) induces the
differentiation of osteoclast precursors into osteoclasts in the
presence of M-CSF. Here, the effects of sODF on the survival,
multinucleation, and pit-forming activity of murine osteoclasts were
examined in comparison with those of M-CSF and IL-1. Osteoclast-like
cells (OCLs) formed in cocultures of murine osteoblasts and bone marrow
cells expressed mRNA of RANK (receptor activator of NF-
B), a
receptor of ODF. The survival of OCLs was enhanced by the addition of
each of sODF, M-CSF, and IL-1. sODF, as well as IL-1, activated NF-B
and c-Jun N-terminal protein kinase (JNK) in OCLs. Like M-CSF and IL-1,
sODF stimulated the survival and multinucleation of prefusion
osteoclasts (pOCs) isolated from the coculture. When pOCs were cultured
on dentine slices, resorption pits were formed on the slices in the
presence of either sODF or IL-1 but not in that of M-CSF. A soluble
form of RANK as well as osteoprotegerin/osteoclastogenesis inhibitory
factor, a decoy receptor of ODF, blocked OCL formation and prevented
the survival, multinucleation, and pit-forming activity of pOCs induced
by sODF. These results suggest that ODF regulates not only osteoclast
differentiation but also osteoclast function in mice through the
receptor RANK.
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S. E. Lee, W. J. Chung, H. B. Kwak, C.-H. Chung, K. Kwack, Z. H. Lee, and H.-H. Kim Tumor Necrosis Factor-alpha Supports the Survival of Osteoclasts through the Activation of Akt and ERK J. Biol. Chem., December 21, 2001; 276(52): 49343 - 49349. [Abstract] [Full Text] [PDF]
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 N. K. Shevde, A. C. Bendixen, K. M. Dienger, and J. W. Pike Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression PNAS, July 5, 2000; 97(14): 7829 - 7834. [Abstract] [Full Text] [PDF]
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R. N. Pearse, E. M. Sordillo, S. Yaccoby, B. R. Wong, D. F. Liau, N. Colman, J. Michaeli, J. Epstein, and Y. Choi Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression PNAS, September 25, 2001; 98(20): 11581 - 11586. [Abstract] [Full Text] [PDF]
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