The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Single and combined inhibition of tumor necrosis factor, interleukin‐1, and RANKL pathways in tumor necrosis factor–induced arthritis: Effects on synovial inflammation, bone erosion, and cartilage destruction
Abstract
Objective: To investigate the efficacy of single and combined blockade of tumor necrosis factor (TNF), interleukin‐1 (IL‐1), and RANKL pathways on synovial inflammation, bone erosion, and cartilage destruction in a TNF‐driven arthritis model. Methods: Human TNF–transgenic (hTNFtg) mice were treated with anti‐TNF (infliximab), IL‐1 receptor antagonist (IL‐1Ra; anakinra), or osteoprotegerin (OPG; an OPG‐Fc fusion protein), either alone or in combinations of 2 agents or all 3 agents. Synovial inflammation, bone erosion, and cartilage damage were evaluated histologically. Results: Synovial inflammation was inhibited by anti‐TNF (−51%), but not by IL‐1Ra or OPG monotherapy. The combination of anti‐TNF with either IL‐1Ra (−91%) or OPG (−81%) was additive and almost completely blocked inflammation. Bone erosion was effectively blocked by anti‐TNF (−79%) and OPG (−60%), but not by IL‐1Ra monotherapy. The combination of anti‐TNF with IL‐1Ra, however, completely blocked bone erosion (−98%). Inhibition of bone erosion was accompanied by a reduction of osteoclast numbers in synovial tissue. Cartilage destruction was inhibited by anti‐TNF (−43%) and was weakly, but not significantly, inhibited by IL‐1Ra, but was not inhibited by OPG monotherapy. The combination of anti‐TNF with IL‐1Ra was the most effective double combination therapy in preventing cartilage destruction (−80%). In all analyses, the triple combination of anti‐TNF, IL‐1Ra, and OPG was not superior to the double combination of anti‐TNF and IL‐1Ra. Conclusion: Articular changes caused by chronic overexpression of TNF are not completely blockable by monotherapies that target TNF, IL‐1, or RANKL. However, combined approaches, especially the combined blockade of TNF and IL‐1 and, to a lesser extent, TNF and RANKL, lead to almost complete remission of disease. Differences in abilities to block synovial inflammation, bone erosion, and cartilage destruction further strengthen the rationale for using combined blockade of more than one proinflammatory pathway.
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Kong, Y.-Y., Feige, U., Sarosi, I., Bolon, B., Tafuri, A., Morony, S., Capparelli, C., Li, J., Elliott, R., McCabe, S., et al. (1999) · Nature · doi:10.1038/46303 · Cited by 1,856
Self-citationLam, J., Takeshita, S., Barker, J. E., Kanagawa, O., Ross, F. P., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11176 · Cited by 1,440
TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis.
Pettit, A. R., Ji, H., von Stechow, D., Müller, R., Goldring, S. R., Choi, Y., Benoist, C., & Gravallese, E. M. (2001) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63016-7 · Cited by 807
Osteoclasts are essential for TNF-α-mediated joint destruction.
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) · Journal of Clinical Investigation · doi:10.1172/jci0215582 · Cited by 474
Self-citationOsteoprotegerin Reduces Osteoclast Numbers and Prevents Bone Erosion in Collagen-Induced Arthritis
Romas, E., Sims, N. A., Hards, D. K., Lindsay, M., Quinn, J. W. M., Ryan, P. F. J., Dunstan, C. R., Martin, T. J., & Gillespie, M. T. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64417-3 · Cited by 368
Self-citationRedlich, K., Hayer, S., Maier, A., Dunstan, C. R., Tohidast‐Akrad, M., Lang, S., Türk, B., Pietschmann, P., Woloszczuk, W., Haralambous, S., et al. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10097 · Cited by 285
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Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824
Osteoclasts: What Do They Do and How Do They Do It?
Teitelbaum, S. L. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060834 · Cited by 730
Theoleyre, S., Wittrant, Y., Tat, S. K., Fortun, Y., Redini, F., & Heymann, D. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2004.06.004 · Cited by 663
Inflammatory osteolysis: A conspiracy against bone
Mbalaviele, G., Novack, D. V., Schett, G., & Teitelbaum, S. L. (2017) · Journal of Clinical Investigation · doi:10.1172/jci93356 · Cited by 251
Self-citationGeusens, P. P., Landewé, R. B. M., Garnero, P., Chen, D., Dunstan, C. R., Lems, W. F., Stinissen, P., van der Heijde, D. M. F. M., van der Linden, S., & Boers, M. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21896 · Cited by 182
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Metadata
- Authors
- Zwerina, J., Hayer, S., Tohidast‐Akrad, M., Bergmeister, H., Redlich, K., Feige, U., Dunstan, C., Kollias, G., Steiner, G., Smolen, J., & Schett, G.
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2004-01
- Volume
- 50
- Issue
- 1
- Pages
- 277-290
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W1982161161
- Cited by
- 307
- References
- 6
- FWCI
- 17.29
- Type
- journal article
- Language
- en
- Open access
- closed
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- Zwerina, J., Hayer, S., Tohidast‐Akrad, M., Bergmeister, H., Redlich, K., Feige, U., Dunstan, C., Kollias, G., Steiner, G., Smolen, J., & Schett, G. (2004). Single and combined inhibition of tumor necrosis factor, interleukin‐1, and RANKL pathways in tumor necrosis factor–induced arthritis: Effects on synovial inflammation, bone erosion, and cartilage destruction. Arthritis & Rheumatism. https://doi.org/10.1002/art.11487
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