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Melanoma Inhibitory Activity, a biomarker related to chondrocyte anabolism, is reversibly suppressed by proinflammatory cytokines in rheumatoid arthritis
  1. Bernard Vandooren
  1. AMC/UvA, Netherlands
    1. Tineke Cantaert
    1. AMC/UvA, Netherlands
      1. Marie-José van Lierop
      1. Organon NV, Netherlands
        1. Ebo Bos
        1. Organon NV, Netherlands
          1. Leen De Rycke
          1. AMC/UvA, Netherlands
            1. Eric M Veys
            1. Ghent University Hospital, Belgium
              1. Filip De Keyser
              1. Ghent University Hospital, Belgium
                1. Barry Bresnihan
                1. St. Vincents Hopsital, Eire
                  1. Frank P Luyten
                  1. University Hopsitals Leuven, Belgium
                    1. Peter C Verdonk
                    1. Ghent University Hospital, Belgium
                      1. Paul P Tak
                      1. AMC/UvA, Netherlands
                        1. Annemieke H Boots
                        1. Organon NV, Netherlands
                          1. Dominique Baeten (d.l.baeten{at}amc.uva.nl)
                          1. AMC/UvA, Netherlands

                            Abstract

                            Objective: In mice, melanoma inhibitory activity (MIA) is a chondrocyte-specific molecule with a similar regulation as collagen type II. As MIA is a small secreted protein, we assessed its value as cartilage biomarker in human inflammatory arthritis.

                            Methods: MIA tissue distribution was studied by quantitative-PCR and immunohistochemistry. The regulation of MIA production was studied in vivo in rheumatoid arthritis (RA)(n=37) and spondyloarthritis (SpA)(n=30) synovial fluid (SF) and in vitro in alginate embedded human chondrocytes. Therapeutic modulation of serum MIA was evaluated during TNF-alpha and IL-1 blockade in RA.

                            Results: MIA was primarily expressed by chondrocytes in the human joint. SF MIA levels were lower in RA than in SpA despite similar levels of overall synovial inflammation. Further analysis indicated that these levels were inversely correlated with the degree of joint inflammation in RA but not in SpA and that the levels of TNF alpha and IL-1 beta were significantly increased in RA versus SpA. Accordingly, these proinflammatory cytokines suppressed MIA mRNA and protein in cultured chondrocytes. This suppression was paralleled by suppression of cartilage anabolism as assessed by collagen type 2 and aggrecan mRNA. Treatment of RA patients with TNF-blockade or IL-1 blockade induced an increase of serum MIA levels.

                            Conclusion: The decreased levels of MIA in the inflamed RA joint and the co-regulation of MIA and cartilage matrix molecules by proinflammatory cytokines indicate that joint inflammation in RA does not only drive accelerated cartilage degradation but also suppress cartilage anabolism. This inflammation-driven suppression is reversible in vivo.

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