Osteoclast Differentiation Factor is a Ligand for Osteoprotegerin/Osteoclastogenesis-Inhibitory Factor and is Identical to TRANCE/RANKL Export

@article{citeulike:3581401, abstract = {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.<p>}, author = {Yasuda, H. and Shima, N. and Nakagawa, N. and Yamaguchi, K. and Kinosaki, M. and Mochizuki, S. I. and Tomoyasu, A. and Yano, K. and Goto, M. and Murakami, A. and Tsuda, E. and Morinaga, T. and Higashio, K. and Udagawa, N. and Takahashi, N. and Suda, T.}, citeulike-article-id = {3581401}, citeulike-linkout-0 = {http://adsabs.harvard.edu/cgi-bin/nph-bib_query?bibcode=1998PNAS...95.3597Y}, journal = {Proceedings of the National Academy of Science}, keywords = {bmu, bone, opg, osteoclast, pathway, rankl, remodeling}, month = {March}, pages = {3597--3602}, posted-at = {2008-11-20 07:16:08}, priority = {2}, title = {Osteoclast Differentiation Factor is a Ligand for Osteoprotegerin/Osteoclastogenesis-Inhibitory Factor and is Identical to TRANCE/RANKL}, url = {http://adsabs.harvard.edu/cgi-bin/nph-bib_query?bibcode=1998PNAS...95.3597Y}, volume = {95}, year = {1998} }

TY - JOUR ID - citeulike:3581401 L3 - citeulike-article-id:3581401 N2 - 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.<p> JF - Proceedings of the National Academy of Science EP - 3602 TI - Osteoclast Differentiation Factor is a Ligand for Osteoprotegerin/Osteoclastogenesis-Inhibitory Factor and is Identical to TRANCE/RANKL VL - 95 SP - 3597 KW - bmu KW - bone KW - opg KW - osteoclast KW - pathway KW - rankl KW - remodeling AU - Yasuda, H AU - Shima, N AU - Nakagawa, N AU - Yamaguchi, K AU - Kinosaki, M AU - Mochizuki, SI AU - Tomoyasu, A AU - Yano, K AU - Goto, M AU - Murakami, A AU - Tsuda, E AU - Morinaga, T AU - Higashio, K AU - Udagawa, N AU - Takahashi, N AU - Suda, T PY - 1998/March// UR - http://adsabs.harvard.edu/cgi-bin/nph-bib_query?bibcode=1998PNAS...95.3597Y ER -