title: TNF-alpha and pathologic bone resorption.
abstract: Chronic inflammatory bone diseases, such as rheumatoid arthritis, periodontal disease and aseptic periprosthetic osteolysis, are characterized by bone loss around affected joints and teeth caused by increased osteoclastic bone resorption. This resorption is mediated largely by the increased local production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFa). These cytokines may induce resorption indirectly by affecting the production of the essential osteoclast differentiation factor, receptor activator of NF-kB ligand, and/or its soluble decoy receptor, osteoprotegerin, by osteoblast/stromal cells or directly by enhancing proliferation and/or activity of cells in the osteoclast lineage. The importance of TNFa in the pathogenesis of various forms of bone loss is supported by both experimental and clinical evidence. However, TNFa is not absolutely required for osteoclastogenesis, erosive arthritis, or osteolysis, as all these events could occur in the absence of TNFa and whether TNFa promotes osteoclast formation independently of RANK signaling is still a topic of debate. Here we review our current understanding of the mechanisms whereby TNFa increases osteoclastogenesis in vitro and in vivo.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. Brendan_Boyce@URMC.Rochester.Edu
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Boyce
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Yao
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: I Raul
authors.initials: IR
authors.lastname: Badell
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: Lianping
authors.initials: L
authors.lastname: Xing
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology; D001862:Bone Resorption / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D010010:Osteoclasts / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha