{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:29:10Z","timestamp":1791268150305,"version":"4.1.0"},"reference-count":31,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,8,21]]},"abstract":"<jats:p>High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts. We demonstrate that both intravenous injection of recombinant OPG protein and transgenic overexpression of OPG in OPG\u2212\/2 mice effectively rescue the osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous injection of recombinant OPG over a 4-wk period could not reverse the arterial calcification observed in OPG\u2212\/\u2212 mice. In contrast, transgenic OPG delivered from mid-gestation through adulthood does prevent the formation of arterial calcification in OPG\u2212\/\u2212 mice. Although OPG is normally expressed in arteries, OPG ligand (OPGL) and receptor activator of NF-\u03baB (RANK) are not detected in the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK transcripts are detected in the calcified arteries of OPG\u2212\/\u2212 mice. Furthermore, RANK transcript expression coincides with the presence of multinuclear osteoclast-like cells. These findings indicate that the OPG\/OPGL\/RANK signaling pathway may play an important role in both pathological and physiological calcification processes. Such findings may also explain the observed high clinical incidence of vascular calcification in the osteoporotic patient population.<\/jats:p>","DOI":"10.1084\/jem.192.4.463","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"463-474","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":430,"title":["Osteoprotegerin Reverses Osteoporosis by Inhibiting Endosteal Osteoclasts and Prevents Vascular Calcification by Blocking a Process Resembling Osteoclastogenesis"],"prefix":"10.1084","volume":"192","author":[{"given":"Hosung","family":"Min","sequence":"first","affiliation":[{"name":"aDepartment of Biosystems Analysis, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Morony","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko","family":"Sarosi","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin R.","family":"Dunstan","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Capparelli","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Scully","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwyneth","family":"Van","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Kaufman","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Kostenuik","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Lacey","sequence":"additional","affiliation":[{"name":"bDepartment of Pharmacology\/Pathology, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Boyle","sequence":"additional","affiliation":[{"name":"cDepartment of Inflammation, Amgen, Incorporated, Thousand Oaks, California 91320"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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