Expression of WISP-1 (ccn4), WISP-2 (ccn5) and WISP-3 (ccn6) in Rheumatoid Arthritic Synovium Evaluated by DNA Microarrays

  • Mori Hiroki
    Department of Clinical Diagnosis, Shujitsu University School of Pharmacy
  • Nishida Keiichiro
    Department of Orthopaedics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Ozaki Toshifumi
    Department of Orthopaedics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Inoue Hajime
    Department of Orthopaedics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Setsu Kojun
    Laboratories for Structure and Function of Pharmaceutical Sciences, Tokushima Bunri University
  • Tsujigiwa Hidetsugu
    Deparment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Nagatsuka Hitoshi
    Deparment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Gunduz Mehmet
    Deparment of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
  • Nakanishi Tohru
    Department of Clinical Diagnosis, Shujitsu University School of Pharmacy

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Rheumatoid disease (RA) is one of the complex diseases that showed multiple progression stages. At first inflammatory response is occurred by self antibodies, and then the proliferation of synoviocytes is abnormally promoted. These synoviocytes invade into articular structures and finally articular cartilage is destroyed. In order to analyze growth-promoting factors in synovial cells from articular tissues of RA, we performed DNA microarray analysis and compared the expression patterns of their mRNA to that of synoviocytes from osteoarthritis (OA). The results showed that the expression of many genes was up-regulated in RA synoviocytes comparing with OA synoviocytes. Among these genes, RT-PCR analysis revealed that Wnt-1-induced secreted protein 2 (WISP-2, CCN5) and protein 3 (WISP-3, CCN6) which are belong to the novel gene family, CCN, were highly up-regulated in RA synoviocytes. In addition, one truncated isoform of WISP-3 which may be related to the ongoing of some type of RA, was detected in RA synoviocytes. Furthermore, immunohistochemical analysis showed that the products of both CCN genes were highly distributed in active synoviocytes of articular tissues of RA. These results indicate that both CCN genes and their products play some roles in the progression of RA.

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