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Osteoclasts are essential for TNF-alpha-mediated joint destruction

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Osteoclasts are essential for TNF-alpha-mediated joint destruction. / Redlich, Kurt; Hayer, Silvia; Ricci, Romeo; David, Jean-Pierre; Tohidast-Akrad, Makiyeh; Kollias, George; Steiner, Günter; Smolen, Josef S; Wagner, Erwin F; Schett, Georg.

In: J CLIN INVEST, Vol. 110, No. 10, 01.11.2002, p. 1419-27.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Redlich, K, Hayer, S, Ricci, R, David, J-P, Tohidast-Akrad, M, Kollias, G, Steiner, G, Smolen, JS, Wagner, EF & Schett, G 2002, 'Osteoclasts are essential for TNF-alpha-mediated joint destruction', J CLIN INVEST, vol. 110, no. 10, pp. 1419-27. https://doi.org/10.1172/JCI15582

APA

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-alpha-mediated joint destruction. J CLIN INVEST, 110(10), 1419-27. https://doi.org/10.1172/JCI15582

Vancouver

Redlich K, Hayer S, Ricci R, David J-P, Tohidast-Akrad M, Kollias G et al. Osteoclasts are essential for TNF-alpha-mediated joint destruction. J CLIN INVEST. 2002 Nov 1;110(10):1419-27. https://doi.org/10.1172/JCI15582

Bibtex

@article{5fa5e127006146deb0c556fec83e80e9,
title = "Osteoclasts are essential for TNF-alpha-mediated joint destruction",
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.",
keywords = "Animals, Arthritis, Rheumatoid, Carrier Proteins, Collagenases, Genes, fos, Humans, Matrix Metalloproteinase 13, Matrix Metalloproteinase 3, Matrix Metalloproteinase 9, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Osteoclasts, Osteopetrosis, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Tumor Necrosis Factor-alpha",
author = "Kurt Redlich and Silvia Hayer and Romeo Ricci and Jean-Pierre David and Makiyeh Tohidast-Akrad and George Kollias and G{\"u}nter Steiner and Smolen, {Josef S} and Wagner, {Erwin F} and Georg Schett",
year = "2002",
month = nov,
day = "1",
doi = "10.1172/JCI15582",
language = "English",
volume = "110",
pages = "1419--27",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "10",

}

RIS

TY - JOUR

T1 - Osteoclasts are essential for TNF-alpha-mediated joint destruction

AU - Redlich, Kurt

AU - Hayer, Silvia

AU - Ricci, Romeo

AU - David, Jean-Pierre

AU - Tohidast-Akrad, Makiyeh

AU - Kollias, George

AU - Steiner, Günter

AU - Smolen, Josef S

AU - Wagner, Erwin F

AU - Schett, Georg

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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.

AB - 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.

KW - Animals

KW - Arthritis, Rheumatoid

KW - Carrier Proteins

KW - Collagenases

KW - Genes, fos

KW - Humans

KW - Matrix Metalloproteinase 13

KW - Matrix Metalloproteinase 3

KW - Matrix Metalloproteinase 9

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Osteoclasts

KW - Osteopetrosis

KW - RANK Ligand

KW - Receptor Activator of Nuclear Factor-kappa B

KW - Tumor Necrosis Factor-alpha

U2 - 10.1172/JCI15582

DO - 10.1172/JCI15582

M3 - SCORING: Journal article

C2 - 12438440

VL - 110

SP - 1419

EP - 1427

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 10

ER -