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

Open access
Kobayashi, Kanichiro, Takahashi, Naoyuki, Jimi, Eijiro, Udagawa, Nobuyuki, Takami, Masamichi, Kotake, Shigeru, Nakagawa, Nobuaki, Kinosaki, Masahiko, Yamaguchi, Kyoji, Shima, Nobuyuki, Yasuda, Hisataka, Morinaga, Tomonori, Higashio, Kanji, Martin, T. John, Suda, Tatsuo·2000·The Journal of Experimental Medicine

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-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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Metadata

Authors
Kobayashi, K., Takahashi, N., Jimi, E., Udagawa, N., Takami, M., Kotake, S., Nakagawa, N., Kinosaki, M., Yamaguchi, K., Shima, N., Yasuda, H., Morinaga, T., Higashio, K., Martin, T. J., & Suda, T.
Venue
The Journal of Experimental Medicine
Published
2000-01-17
Volume
191
Issue
2
Pages
275-286
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2131357215
Cited by
1,304
References
6
FWCI
23.54
Type
journal article
Language
en
Open access
bronze

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Kobayashi, K., Takahashi, N., Jimi, E., Udagawa, N., Takami, M., Kotake, S., Nakagawa, N., Kinosaki, M., Yamaguchi, K., Shima, N., Yasuda, H., Morinaga, T., Higashio, K., Martin, T. J., & Suda, T. (2000). Tumor Necrosis Factor α Stimulates Osteoclast Differentiation by a Mechanism Independent of the Odf/Rankl–Rank Interaction. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.191.2.275

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