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http://purl.uniprot.org/citations/14969390http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14969390http://www.w3.org/2000/01/rdf-schema#comment"

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To address the controversy of whether TNFalpha can compensate for RANKL in osteoclastogenesis in vivo, we used a TNFalpha-induced animal model of inflammatory arthritis and blocked RANKL/RANK signaling. TNFalpha increased osteoclast precursors available for RANK-dependent osteoclastogenesis. RANK signaling is not required for the TNFalpha-stimulated increase in CD11b(hi) osteoclast precursors but is essential for mature osteoclast formation.

Introduction

Although critical roles of TNFalpha in inflammatory arthritis and RANKL in bone resorption have been firmly established, a central controversy remains about the extent to which TNFalpha can compensate for RANKL during osteoclastogenesis and the stage at which RANK signaling is required for osteoclastogenesis. Here, we used the human TNFalpha transgenic mouse model (TNF-Tg) of erosive arthritis to determine if there are both RANK-dependent and -independent stages of osteoclastogenesis in TNFalpha-induced erosive arthritis.

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 X RANK -/-mice generated by crossing TNF-Tg mice with RANK-/-mice.

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 CD11b(hi) OCP numbers in their spleens. Long-term RANK:Fc administration alleviated joint erosion. Furthermore, TNF-Tg x RANK -/-mice had severe osteopetrosis, no osteoclasts, and no joint erosion, but increased CD11b(hi) precursor numbers that failed to form mature osteoclasts in vitro.

Conclusion

RANK signaling is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis but not for the TNFalpha-induced increase in CD11b(hi) OCP that subsequently can differentiate into osteoclasts in inflamed joints."xsd:string
http://purl.uniprot.org/citations/14969390http://purl.org/dc/terms/identifier"doi:10.1359/jbmr.0301233"xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/author"Li P."xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/author"Ma L."xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/author"Xing L."xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/author"Schwarz E.M."xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/author"Boyce B.F."xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/author"O'Keefe R.J."xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/name"J Bone Miner Res"xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/pages"207-213"xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/title"RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis."xsd:string
http://purl.uniprot.org/citations/14969390http://purl.uniprot.org/core/volume"19"xsd:string
http://purl.uniprot.org/citations/14969390http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/14969390
http://purl.uniprot.org/citations/14969390http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/14969390
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http://purl.uniprot.org/uniprot/#_O35305-mappedCitation-14969390http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/14969390
http://purl.uniprot.org/uniprot/#_Q3U593-mappedCitation-14969390http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/14969390
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http://purl.uniprot.org/uniprot/#_Q3U4I6-mappedCitation-14969390http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/14969390
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