The DOI matches its Crossref record.
Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation
Abstract
Chronic immune responses and inflammatory reactions in rheumatoid arthritis (RA) often cause severe destruction of cartilage and bone, but its mechanism is still a matter of controversy. We reported that interleukin-6 (IL-6) alone does not induce osteoclast formation, but soluble interleukin-6 receptors (sIL-6R) triggered the formation in the presence of IL-6 in cocultures of murine osteoblastic cells and bone marrow cells. In this study, we examined the involvement of sIL-6R and IL-6 in joint destruction in patients with RA. Although the frequency of patients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) and osteoarthritis (OA) patients (43%), the number of osteoclast-like cells found in the synovium was greater in the former than in the latter. Multinucleated cells obtained from RA synovium expressed the osteoclast-specific phenotype such as tartrate-resistant acid phosphatase, carbonic anhydrase II, vacuolar proton-ATPase and vitronectin receptors at similar levels to those from a human giant cell tumor of bone. The concentration of both IL-6 and sIL-6R was significantly higher in the synovial fluids from patients with RA than with OA. The concentration of IL-6 and sIL-6R correlated well with the roentgenologic grades of joint destruction. Dose-response curves for human IL-6 and human sIL-6R in inducing osteoclast-like cell formation in cocultures indicated that the RA synovial fluids contained sufficient IL-6 and sIL-6R to induce osteoclastogenesis. When synovial fluids from RA and OA patients were added to the cocultures, some of the RA synovial fluids containing high levels of IL-6 and sIL-6R stimulated osteoclast-like cell formation, which was strikingly inhibited by adding anti-IL-6R antibody simultaneously. These results suggest that IL-6 in the RA synovial fluids is at least in part responsible for joint destruction in the presence of sIL-6R through osteoclastogenesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cited by
IL‐6 in inflammation, immunity, and disease
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016295 · Cited by 5,046
Self-citationTherapeutic Approaches to Bone Diseases
Rodan, G. A., & Martin, T. J. (2000) · Science · doi:10.1126/science.289.5484.1508 · Cited by 1,767
The Pathophysiologic Roles of Interleukin-6 in Human Disease
Papanicolaou, D. A., Wilder, R. L., Manolagas, S. C., & Chrousos, G. P. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-2-199801150-00009 · Cited by 1,146
Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer
Jones, S. A., & Jenkins, B. J. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0066-7 · Cited by 1,102
Holt, S. C., & Ebersole, J. L. (2005) · Periodontology 2000 · doi:10.1111/j.1600-0757.2005.00113.x · Cited by 932
Maini, R. N., Taylor, P. C., Szechinski, J., Pavelka, K., Bröll, J., Balint, G., Emery, P., Raemen, F., Petersen, J., Smolen, J., et al. (2006) · Arthritis & Rheumatism · doi:10.1002/art.22033 · Cited by 790
Self-citationInterleukin 6 is required for the development of collagen-induced arthritis
Alonzi, T., Fattori, E., Lazzaro, D., Costa, P., Probert, L., Kollias, G., De Benedetti, F., Poli, V., & Ciliberto, G. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.4.461 · Cited by 604
Choy, E. H. S., Isenberg, D. A., Garrood, T., Farrow, S., Ioannou, Y., Bird, H., Cheung, N., Williams, B., Hazleman, B., Price, R., et al. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10623 · Cited by 526
Self-citationInterleukin 6 plays a key role in the development of antigen-induced arthritis
Ohshima, S., Saeki, Y., Mima, T., Sasai, M., Nishioka, K., Nomura, S., Kopf, M., Katada, Y., Tanaka, T., Suemura, M., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8222 · Cited by 406
Self-citationRichardson, D., Pearson, R. G., Kurian, N., Latif, M. L., Garle, M. J., Barrett, D. A., Kendall, D. A., Scammell, B. E., Reeve, A. J., & Chapman, V. (2008) · Arthritis Research & Therapy · doi:10.1186/ar2401 · Cited by 303
Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo
Axmann, R., Böhm, C., Krönke, G., Zwerina, J., Smolen, J., & Schett, G. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24781 · Cited by 263
Nowell, M. A., Williams, A. S., Carty, S. A., Scheller, J., Hayes, A. J., Jones, G. W., Richards, P. J., Slinn, S., Ernst, M., Jenkins, B. J., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.182.1.613 · Cited by 215
Pillinger, T., Osimo, E. F., Brugger, S., Mondelli, V., McCutcheon, R. A., & Howes, O. D. (2019) · Schizophrenia Bulletin · doi:10.1093/schbul/sby160 · Cited by 190
Crotti, T. N., Smith, M. D., Weedon, H., Ahern, M. J., Findlay, D. M., Kraan, M., Tak, P. P., & Haynes, D. R. (2002) · Annals of the Rheumatic Diseases · doi:10.1136/ard.61.12.1047 · Cited by 186
IL-1 and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase.
Kumar, S., Votta, B. J., Rieman, D. J., Badger, A. M., Gowen, M., & Lee, J. C. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.1082 · Cited by 107
Tsangari, H., Findlay, D. M., Kuliwaba, J. S., Atkins, G. J., & Fazzalari, N. L. (2004) · Bone · doi:10.1016/j.bone.2004.02.006 · Cited by 69
Safety and efficacy of tocilizumab for the treatment of rheumatoid arthritis
Ogata, A., Hirano, T., Hishitani, Y., & Tanaka, T. (2012) · Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders · doi:10.4137/cmamd.s7371 · Cited by 61
Effect of carbohydrate feeding on the bone metabolic response to running
Sale, C., Varley, I., Jones, T. W., James, R. M., Tang, J. C. Y., Fraser, W. D., & Greeves, J. P. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00241.2015 · Cited by 57
Taves, S., Sun, J., Livingston, E. W., Chen, X., Amiaud, J., Brion, R., Hannah, W. B., Bateman, T. A., Heymann, D., & Monahan, P. E. (2019) · Scientific Reports · doi:10.1038/s41598-019-50787-9 · Cited by 26
Honda, K. (2011) · Journal of Oral Science · doi:10.2334/josnusd.53.87 · Cited by 15
Metadata
- Authors
- Kotake, S., Sato, K., Kim, K. J., Takahashi, N., Udagawa, N., Nakamura, I., Yamaguchi, A., Kishimoto, T., Suda, T., & Kashiwazaki, S.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-01-01
- Volume
- 11
- Issue
- 1
- Pages
- 88-95
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2044561904
- Cited by
- 545
- References
- 0
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
