Tumor necrosis factor α stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL–RANK interaction

K Kobayashi, N Takahashi, E Jimi… - The Journal of …, 2000 - rupress.org
K Kobayashi, N Takahashi, E Jimi, N Udagawa, M Takami, S Kotake, N Nakagawa…
The Journal of experimental medicine, 2000rupress.org
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-BMMφ) appeared within 3 d. Tartrate-resistant acid
phosphatase–positive osteoclasts were also formed when M-BMMφ were further cultured for …
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-BMMφ) appeared within 3 d. Tartrate-resistant acid phosphatase–positive osteoclasts were also formed when M-BMMφ were further cultured for 3 d with mouse tumor necrosis factor α (TNF-α) in the presence of M-CSF. Osteoclast formation induced by TNF-α 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-BMMφ prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-α. Osteoclasts induced by TNF-α formed resorption pits on dentine slices only in the presence of IL-1α. These results demonstrate that TNF-α stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL–RANK system. TNF-α together with IL-1α may play an important role in bone resorption of inflammatory bone diseases.
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