title: Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction.
abstract: Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the differentiation of osteoclast progenitors of the monocyte/macrophage lineage into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF, also called CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF-dependent bone marrow macrophages (M-BMM phi) appeared within 3 d. Tartrate-resistant acid phosphatase-positive osteoclasts were also formed when M-BMM phi were further cultured for 3 d with mouse tumor necrosis factor alpha (TNF-alpha) in the presence of M-CSF. Osteoclast formation induced by TNF-alpha was inhibited by the addition of respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not by osteoclastogenesis inhibitory factor (OCIF, also called OPG, a decoy receptor of ODF/RANKL), nor the Fab fragment of anti-RANK (ODF/RANKL receptor) antibody. Experiments using M-BMM phi prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-alpha. Osteoclasts induced by TNF-alpha formed resorption pits on dentine slices only in the presence of IL-1alpha. These results demonstrate that TNF-alpha stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL-RANK system. TNF-alpha together with IL-1alpha may play an important role in bone resorption of inflammatory bone diseases.
authors.affiliation: Department of Biochemistry, School of Dentistry, Showa University, Tokyo 142-8555, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: E
authors.initials: E
authors.lastname: Jimi
authors.forename: N
authors.initials: N
authors.lastname: Udagawa
authors.forename: M
authors.initials: M
authors.lastname: Takami
authors.forename: S
authors.initials: S
authors.lastname: Kotake
authors.forename: N
authors.initials: N
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Kinosaki
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Shima
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Morinaga
authors.forename: K
authors.initials: K
authors.lastname: Higashio
authors.forename: T J
authors.initials: TJ
authors.lastname: Martin
authors.forename: T
authors.initials: T
authors.lastname: Suda
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D007375:Interleukin-1; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase