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Overexpression of Osteopontin in Rheumatoid Synovial Mononuclear Cells Is Associated with Joint Inflammation, Not with Genetic Polymorphism
GUANGWU XU, WEI SUN, DONGYI HE, LI WANG, WENXIN ZHENG, HONG NIE, LIQING NI, DONGQING ZHANG, NINGLI LI, and JINGWU ZHANG
ABSTRACT. Objective. Osteopontin (OPN) is thought to play an important role in rheumatoid synovitis. We investigated the expression of OPN in rheumatoid synovial fluid mononuclear cells (SFMC) and its potential association with genetic polymorphism of the OPN gene and joint inflammation in rheumatoid arthritis (RA). Methods. 1. The expression of OPN mRNA in peripheral blood mononuclear cells (PBMC) and SFMC of patients with RA was analyzed quantitatively by real-time polymerase chain reaction (PCR). Results were analyzed in paired PBMC and SFMC and control PBMC. 2. Six single nuclear acid polymorphisms of the OPN gene were genotyped in a cohort of 192 Chinese patients with RA and controls (n = 288) by restriction fragment length polymorphism PCR or direct DNA sequencing. 3. SF derived from RA patients was examined for the stimulating effect on mRNA expression of the OPN gene in PBMC. Results. The expression of OPN gene was significantly increased in SFMC and, to a lesser degree, in PBMC of patients with RA compared to control PBMC (p < 0.01). However, the prevalence of OPN genotype and allele frequencies at the selected positions did not differ significantly between RA patients and the control group (p > 0.05). Further characterization indicated that SF known to contain a variety of proinflammatory factors significantly stimulated mRNA expression of OPN in PBMC obtained from RA patients or healthy controls. Conclusion. Overexpression of OPN mRNA in SFMC is associated with proinflammatory factors produced in inflamed joints, but not with OPN genetic polymorphisms. OPN gene polymorphisms do not correlate with susceptibility to RA. (J Rheumatol 2005;32:410-6) Key Indexing Terms:
OSTEOPONTIN
From the Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Second Medical University, Shanghai Institute of Immunology and E-Institute of Shanghai Universities, Shanghai; Guanghua Rheumatology Hospital, Shanghai, China; and Department of Immunology, Baylor College of Medicine, Houston, Texas, USA. Supported by grants from Chinese Academy of Sciences Knowledge Innovation Program (KSCX2-SW-212) and the National High Technology Research and Development Program of China (863 Program 2002AA216121), National Natural Science Foundation (30430650), and Shanghai Commission of Science and Technology (04DZ14902, 04DZ19202, 04JC14040, 03 XD 14015). G-W. Xu, MD, PhD; W. Sun, MD, PhD; W-X. Zheng, MD; H. Nie, MD, PhD; N-L. Li, MD, PhD, Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Institute of Immunology; D-Y. He, MD; L-Q. Ni, MD, Guanghua Rheumatology Hospital; L. Wang, BS; D-Q. Zhang, MD, PhD, Shanghai Institute of Immunology, Shanghai Second Medical University; J-W. Zhang, MD, PhD, Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Institute of Immunology, Shanghai Second Medical University E-Institute of Shanghai Universities, Department of Immunology, Baylor College of Medicine. Address reprint requests to Dr. J-W. Zhang, Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Mail Station NB302, Houston, TX 77030. E-mail: jzang@bcm.tmc.edu Received July 13, 2004; revision accepted October 12, 2004. |