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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Figure 1

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Expression of OPN mRNA in T cells derived from peripheral blood, SF, and...
Expression of OPN mRNA in T cells derived from peripheral blood, SF, and ST. (A) RNA was extracted from T cells isolated from paired SF, ST, and peripheral blood of RA patients (n = 32) for real-time PCR analysis. A panel of control T cell preparations was obtained from 31 healthy individuals. OPN expression was normalized to endogenously expressed GAPDH in the same samples. Relative expression was calculated as the difference (ΔΔCT) between the ΔCT values of the test sample and of the endogenous control (GAPDH). Relative expression of OPN gene was calculated and expressed as 2–ΔΔCT (see Methods). (B) CD4+ T cells and CD8+ T cells were isolated from the same T cell preparations of SF specimens by magnetic bead separation and were analyzed for OPN expression by real-time PCR. The purity of the resulting T cell preparations was greater than 97%. The data represent the mean of 6 randomly selected individual T cell preparations. In all cases, asterisks indicate statistically significant differences between the groups (P < 0.05).