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Enhanced Local Production of Osteopontin in Rheumatoid Joints
SHIRO OHSHIMA, NORIHIKO YAMAGUCHI, KATSUHIRO NISHIOKA, TORU MIMA, TAEKO ISHII, MITSUKO UMESHITA-SASAI, HIDEYUKI KOBAYASHI, MASATOSHI SHIMIZU, YOSHINORI KATADA, SHIGEYUKI WAKITANI, NORIKAZU MURATA, SHINTARO NOMURA, HIROAKI MATSUNO, RIE KATAYAMA, SHIGEYUKI KON, MANABU INOBE, TOSHIMITSU UEDE, ICHIRO KAWASE, and YUKIHIKO SAEKI
ABSTRACT.
Methods. Localization of OPN in the rheumatoid synovium was examined by immunohistochemistry. In vitro OPN production by cultured synovial cells from patients with RA (n = 5) and with osteoarthritis (OA) (n = 5) was assessed by ELISA. OPN concentrations in plasma and synovium were quantified in patients with RA (n = 23) by 2 distinct ELISA systems to measure both thrombin cleaved and non-cleaved OPN. The same experiments were done in patients with OA (n = 15) and healthy volunteers (n = 10) as a control. Results. OPN was highly detected by immunohistochemistry predominantly in the RA synovial lining cells, while less and scattered OPN was detected in OA synovial tissues. ELISA revealed that cultured RA synovial cells secreted significantly more OPN than OA cells. ELISA also showed a marked increase of OPN levels in synovial fluid (SF) of patients with RA and with OA compared to the control plasma OPN levels, although OPN levels were not increased in RA and OA plasma compared to healthy controls. SF OPN levels of patients with RA were significantly higher than those of patients with OA, and correlated with serum C-reactive protein levels. The ratios of thrombin cleaved versus non-cleaved OPN were significantly increased in RA plasma and SF compared with OA plasma and SF and plasma from healthy controls. Conclusion. Our results revealed enhanced local production of OPN in rheumatoid joints, suggesting involvement of OPN in the pathogenesis of RA. (J Rheumatol 2002;29:2061-7) Key Indexing Terms:
OSTEOPONTIN
From the Department of Molecular Medicine and Department of Pathology, Osaka University Medical School, Osaka; Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo; Osaka-Minami National Hospital, Kawachinagano; Tokyo Research Laboratories, Tokyo; Department of Orthopedic Surgery, Toyama Medical and Pharmaceutical University, Toyama; Immuno-Biological Laboratories, Naka, Fujioka; and Hino Clinic, Sakai, Japan. Supported in part by grants from the Ministry of Education, Science and Culture, the Ministry of Health and Welfare of Japan, Kowa Pharmaceutical Company, and Ono Pharmaceutical Company. S. Ohshima, MD; N. Yamaguchi, MD; K. Nishioka, MD; T. Mima, MD; T. Ishii, MD; M. Umeshita-Sasai, MD, Department of Molecular Medicine, Osaka University Medical School; H. Kobayashi, BS, Department of Molecular Medicine, Osaka University Medical School and Kowa Co. Ltd.; M. Shimizu, MD, Hino Clinic; Y. Katada, MD; S. Wakitani, MD; N. Murata, MD, Osaka-Minami National Hospital; S. Nomura, PhD, Department of Pathology, Osaka University Medical School; H. Matsuno, MD; R. Katayama, MD, Department of Orthopedic Surgery, Toyama Medical and Pharmaceutical University; S. Kon, PhD, Immuno-Biological Laboratories; M. Inobe, MD; T. Uede, MD, Institute for Genetic Medicine, Hokkaido University; I. Kawase, MD; Y. Saeki, MD, Department of Molecular Medicine, Osaka University Medical School. Address reprint requests to Dr. Y. Saeki, Department of Molecular Medicine, Osaka University Medical School, 2-2 Yamada-Oka, Suita City, Osaka 565-0871, Japan. E-mail: saekiy@imed3.med.osaka-u.ac.jp Submitted May 1, 2001; revision accepted April 15, 2002. |