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Cited by 531

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Osteoclasts are essential for TNF-α–mediated joint destruction

Open access
Redlich, Kurt, Hayer, Silvia, Ricci, Romeo, David, Jean-Pierre, Tohidast-Akrad, Makiyeh, Kollias, George, Steiner, Günter, Smolen, Josef S., Wagner, Erwin F., Schett, Georg·2002·Journal of Clinical Investigation

Abstract

The detailed cellular and molecular mechanisms leading to joint destruction in rheumatoid arthritis, a disease driven by proinflammatory cytokines, are still unknown. To address the question of whether osteoclasts play a pivotal role in this process, transgenic mice that express human TNF (hTNFtg) and that develop a severe and destructive arthritis were crossed with osteopetrotic, c-fos-deficient mice (c-fos(-/-)) completely lacking osteoclasts. The resulting mutant mice (c-fos(-/-)hTNFtg) developed a TNF-dependent arthritis in the absence of osteoclasts. All clinical features of arthritis, such as paw swelling and reduction of grip strength, progressed equally in both groups. Histological evaluation of joint sections revealed no difference in the extent of synovial inflammation, its cellular composition (except for the lack of osteoclasts), and the expression of matrix metalloprotein-ase-3 (MMP-3) and MMP-13. In addition, cartilage damage, proteoglycan loss, and MMP-3, -9, and -13 expression in chondrocytes were similar in hTNFtg and c-fos(-/-)hTNFtg mice. However, despite the presence of severe inflammatory changes, c-fos(-/-)hTNFtg mice were fully protected against bone destruction. These data reveal that TNF-dependent bone erosion is mediated by osteoclasts and that the absence of osteoclasts alters TNF-mediated arthritis from a destructive to a nondestructive arthritis. Therefore, in addition to the use of anti-inflammatory therapies, osteoclast inhibition could be beneficial for the treatment of rheumatoid arthritis.

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Cites

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Research works printed but not linked: 12

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Metadata

Authors
Redlich, K., Hayer, S., Ricci, R., David, J.-P., Tohidast-Akrad, M., Kollias, G., Steiner, G., Smolen, J. S., Wagner, E. F., & Schett, G.
Venue
Journal of Clinical Investigation
Published
2002-11-15
Volume
110
Issue
10
Pages
1419-1427
ISSN
0021-9738 (ISSN-L)
OpenAlex
W1892597491
Cited by
531
References
47
FWCI
13.12
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Osteoclasts are essential for TNF-α–mediated joint destruction. https://app.cochat.ai/papers/10.1172/jci15582
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Redlich, K., Hayer, S., Ricci, R., David, J.-P., Tohidast-Akrad, M., Kollias, G., Steiner, G., Smolen, J. S., Wagner, E. F., & Schett, G. (2002). Osteoclasts are essential for TNF-α–mediated joint destruction. Journal of Clinical Investigation. https://doi.org/10.1172/jci15582

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