Tumor Necrosis Factor α Stimulates Osteoclast Differentiation by a Mechanism Independent of the Odf/Rankl–Rank Interaction

• DOI: 10.1084/jem.191.2.275
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Kanichiro Kobayashi; Naoyuki Takahashi; Eijiro Jimi; Nobuyuki Udagawa; Masamichi Takami; Shigeru Kotake; Nobuaki Nakagawa; Masahiko Kinosaki; Kyoji Yamaguchi; Nobuyuki Shima; Hisataka Yasuda; Tomonori Morinaga; Kanji Higashio; T. John Martin; Tatsuo Suda
• Keywords: RANK Ligand; Monocyte; Tartrate-resistant acid phosphatase

Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the of osteoclast progenitors monocyte/macrophage lineage into osteoclasts in presence macrophage colony-stimulating (M-CSF, CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF–dependent macrophages (M-BMMφ) appeared within 3 d. Tartrate-resistant acid phosphatase–positive formed when M-BMMφ further for d tumor necrosis α (TNF-α) M-CSF. formation induced by TNF-α was inhibited addition respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not osteoclastogenesis inhibitory (OCIF, OPG, a decoy ODF/RANKL), nor Fab fragment anti–RANK (ODF/RANKL receptor) antibody. Experiments using prepared from TNFR1- TNFR2-deficient mice showed that both and TNFR2-induced signals important TNF-α. Osteoclasts resorption pits on dentine slices only IL-1α. These results demonstrate M-CSF through mechanism independent ODF/RANKL–RANK system. together IL-1α may play an role inflammatory diseases.