{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:35:20Z","timestamp":1792708520603,"version":"4.5.0"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,3,30]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>in vivo<\/jats:italic>\n                    . 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\n                    <jats:italic>in vitro<\/jats:italic>\n                    and blocks osteoclast differentiation and activation\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.7.3540","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:07Z","timestamp":1027679707000},"page":"3540-3545","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1342,"title":["Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand"],"prefix":"10.1073","volume":"96","author":[{"given":"Hailing","family":"Hsu","sequence":"first","affiliation":[{"name":"Departments of Cell Biology, Pathology, Protein Chemistry, Process Science, and Computational Biology, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David 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