Role of osteopontin in amplification and perpetuation of rheumatoid synovitis
Guangwu Xu, … , Jian Hong, Jingwu Z. Zhang
Guangwu Xu, … , Jian Hong, Jingwu Z. Zhang
Published April 1, 2005
Citation Information: J Clin Invest. 2005;115(4):1060-1067. https://doi.org/10.1172/JCI23273.
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Role of osteopontin in amplification and perpetuation of rheumatoid synovitis

Abstract

Osteopontin (OPN) is an extracellular matrix protein of pleiotropic properties and has been recently recognized as a potential inflammatory cytokine. In this study, we demonstrate, for the first time to our knowledge, that overexpression of OPN in synovial T cells is associated with local inflammatory milieu and that OPN acts as an important mediator in amplification and perpetuation of rheumatoid synovitis. The study revealed that mRNA expression of OPN was highly elevated in CD4+ synovial T cells derived from patients with RA, which correlated with increased OPN concentrations in synovial fluid (SF). The pattern of OPN overexpression was confined to rheumatoid synovium and correlated with coexpression of selected OPN receptors in synovial T cells, including integrins αv and β1 and CD44. RA-derived SF stimulated the expression of OPN in T cells, which was attributable to IL-10 present in SF and abrogated by anti–IL-10 antibody. Among the more than 300 autoimmune and inflammatory response genes examined, OPN selectively induced the expression of proinflammatory cytokines and chemokines known to promote migration and recruitment of inflammatory cells. Furthermore, it was evident that OPN activated transcription factor NF-κB in mononuclear cells. The study has important implications for understanding the role of OPN in rheumatoid synovitis and other inflammatory conditions.

Authors

Guangwu Xu, Hong Nie, Ningli Li, Wenxin Zheng, Dongqing Zhang, Guozhang Feng, Liqing Ni, Rong Xu, Jian Hong, Jingwu Z. Zhang

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Quantitative real-time PCR analysis of OPN mRNA expression in T cells in...
Quantitative real-time PCR analysis of OPN mRNA expression in T cells in response to treatment with RA-SF. (A) Prefiltered SF of an RA patient was added, at a final dilution of 1:5, to cultures of PBMCs derived from 10 randomly selected RA patients and 10 healthy individuals matched for age and sex, respectively. After 48-hour incubation, cells were collected and CD2+ T cells were isolated for real-time PCR analysis of OPN expression. The purity of CD2+ T cells was greater than 97%. The data are representative of 4 separate experiments with SF specimens of different RA patients. (B) The dose-response pattern of OPN expression of the same PBMC specimens of RA patients (n = 10) in response to the indicated dilutions of RA SF and paired sera (n = 10) under the same experimental conditions as described in A. The results were reproduced with a panel of 10 purified CD4+ T cell preparations derived from RA patients and healthy individuals. Relative expression of OPN gene was calculated as described in the Figure 1 legend.