Abstract
Osteoblasts or bone marrow stromal cells support osteoclast development through a mechanism of cell-to-cell interaction with osteoclast progenitors. we purified and molecularly cloned osteoclastogenesis-inhibitory factor (OCLF), which turned out to be identical to osteoprotegerin (OPG). OPG/OCIF is a secreted member of the TNF receptor family that inhibits differentiation and activation of osteoclasts. OPG/OCIF specifically bound to a bone marrow stromal cell line, ST2 treated with 1, 25(OH)2D3, but not to untreated cells. To identify a OPG/OCIF ligand, we screened a cDNA expression library of ST2 cells treated with 1,25(OH)2D3 using OPG/OCIF as a probe. The cloned molecule was found to be a member of the membrane-associated TNF ligand family, and it induced osteoclastogenesis in vitro in the absence of osteoblasts/stromal cells. Expression of its gene in osteoblasts/stromal cells was up-regulated by osteotropic factors. Antibody against this protein negated bone resorption elicited by osteotropic factors in a fetal mouse long bone culture system. OPG/OCIF abolished the protein-mediated osteoclastogenesis. We conclude that the protein is osteoclast differentiation factor (ODF), a long-sought mediator responsible for an essential signal to osteoclast progenitors for their differentiation into osteoclasts, and that OPG/OCIF acts as a soluble competitor against ODF receptor that is presumably expressed on osteoclasts and osteoclast progenitors.
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Shima, N. et al. (2002). Osteoclast Differentiation Factor is a Ligand for Osteoprotegerin / Osteoclastogenesis-Inhibitory Factor. In: Ikura, K., Nagao, M., Masuda, S., Sasaki, R. (eds) Animal Cell Technology: Challenges for the 21st Century. Springer, Dordrecht. https://doi.org/10.1007/0-306-46869-7_43
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DOI: https://doi.org/10.1007/0-306-46869-7_43
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