{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:32:17Z","timestamp":1791311537714,"version":"4.3.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To address the controversy of whether TNF\u03b1 can compensate for RANKL in osteoclastogenesis in vivo, we used a TNF\u03b1-induced animal model of inflammatory arthritis and blocked RANKL\/RANK signaling. TNF\u03b1 increased osteoclast precursors available for RANK-dependent osteoclastogenesis. RANK signaling is not required for the TNF\u03b1-stimulated increase in CD11bhi osteoclast precursors but is essential for mature osteoclast formation.<\/jats:p>\n               <jats:p>Introduction: Although critical roles of TNF\u03b1 in inflammatory arthritis and RANKL in bone resorption have been firmly established, a central controversy remains about the extent to which TNF\u03b1 can compensate for RANKL during osteoclastogenesis and the stage at which RANK signaling is required for osteoclastogenesis. Here, we used the human TNF\u03b1 transgenic mouse model (TNF-Tg) of erosive arthritis to determine if there are both RANK-dependent and -independent stages of osteoclastogenesis in TNF\u03b1-induced erosive arthritis.<\/jats:p>\n               <jats:p>Materials and Methods: Osteoclastogenesis and osteoclast precursor (OCP) frequency were analyzed using histology, fluorescence-activated cell sorting (FACS), and cell culture from (1) TNF-Tg mice treated with the RANKL antagonist, RANK:Fc, or (2) TNF-Tg \u00d7 RANK\u2212\/\u2212 mice generated by crossing TNF-Tg mice with RANK\u2212\/\u2212 mice.<\/jats:p>\n               <jats:p>Results: Treatment of TNF-Tg mice, which have increased OCPs in their spleens, with RANK:Fc dramatically reduced osteoclast numbers on the surface of their arthritic joints and within their bones, but did not decrease CD11bhi OCP numbers in their spleens. Long-term RANK:Fc administration alleviated joint erosion. Furthermore, TNF-Tg \u00d7 RANK\u2212\/\u2212 mice had severe osteopetrosis, no osteoclasts, and no joint erosion, but increased CD11bhi precursor numbers that failed to form mature osteoclasts in vitro.<\/jats:p>\n               <jats:p>Conclusion: RANK signaling is essential for mature osteoclast formation in TNF\u03b1-mediated inflammatory arthritis but not for the TNF\u03b1-induced increase in CD11bhi OCP that subsequently can differentiate into osteoclasts in inflamed joints.<\/jats:p>","DOI":"10.1359\/jbmr.0301233","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T06:49:17Z","timestamp":1146120557000},"page":"207-213","source":"Crossref","is-referenced-by-count":195,"title":["RANK Signaling Is Not Required for TNF\u03b1-Mediated Increase in CD11bhi Osteoclast Precursors but Is Essential for Mature Osteoclast Formation in TNF\u03b1-Mediated Inflammatory Arthritis"],"prefix":"10.1093","volume":"19","author":[{"given":"Ping","family":"Li","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M","family":"Schwarz","sequence":"additional","affiliation":[{"name":"The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regis J","family":"O'Keefe","sequence":"additional","affiliation":[{"name":"The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ma","sequence":"additional","affiliation":[{"name":"The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan F","family":"Boyce","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Rochester Medical Center, Rochester, New York, USA"},{"name":"The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianping","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Rochester Medical Center, Rochester, New York, USA"},{"name":"The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019215350900_bib1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and 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