Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand

作者：Hailing Hsu, David L. Lacey, Colin Robert Dunstan, Irina Solovyev, Anne M. Colombero, Emma M. Timms, Hong‐Lin Tan, Gary Elliott, Michael J. Kelley, Ildiko Sarosi, Ling Wang, Xing-Zhong Xia, Robin Elliott, Laura S. Chiu, Tabitha Black, Sheila A. Scully, Casey Capparelli, Sean Morony, Grant T. Shimamoto, Michael Bass, William J. Boyle · 发表于：Proceedings of the National Academy of Sciences · 年份：1999 · DOI：10.1073/pnas.96.7.3540 · 被引用次数：1647 · 研究领域：Bone Metabolism and Diseases、Bone health and treatments、NF-κB Signaling Pathways

A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.