Research from University of Sydney broadens understanding of arthritis

   "After treatment, cells and culture supernatants were collected for zymography, enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blot analysis. Fibroblasts and monocytes from RA patients produced substantially more MMP-9 than did those from OA patients; however, there was no difference in MMP-2 production. The addition of recombinant APC markedly reduced MMP-9 at the gene and protein levels. In contrast, APC up-regulated and activated MMP-2. Using a blocking antibody to the endothelial protein C receptor (EPCR), we showed that the inhibition of MMP-9 by APC was EPCR-dependent. Furthermore, APC directly suppressed the production of tumor necrosis factor (TNF) and the activation of NF-kappa B and MAP kinase p38, and inhibitors of NF-kappa B or p38 reduced the production of MMP-9, suggesting that APC inhibits MMP-9 by blocking TNF, NF-kappa B, and p38. Thus, APC acts on MMP-9 by binding to EPCRs on the cell surface and, subsequently, inhibiting the intracellular activation of the proinflammatory signaling molecules NF-kappa B and p38. APC appears to be the first physiologic agent to inhibit the production of proinflammatory MMP-9, yet increase antiinflammatory MMP-2 activity," wrote M.L. Xue and colleagues, University of Sydney.

   The researchers concluded: "Our results provide the initial evidence that APC may be beneficial in the prevention of inflammation and joint destruction in RA."

   Xue and colleagues published their study in Arthritis and Rheumatism (Research from University of Sydney broadens understanding of arthritis. Arthritis and Rheumatism, 2007;56(9):2864-2874).

   For additional information, contact M.L. Xue, University of Sydney, Royal North Shore Hospital, Institute Bone & Joint Research, Sutton Arthritis Research Laboratory, St. Leonards, NSW 2065, Australia.

   Publisher contact information for the journal Arthritis and Rheumatism is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

   Keywords: Australia, Antiinflammatory, Arthritis, Biotechnology, Diagnosis, Diagnostics, Enzyme Research, Gene Therapy, Matrix Metalloproteinase, Metalloproteinases, Osteoarthritis, Polymerase, Proteins, Proteomics, Rheumatism, Rheumatoid Arthritis, Treatment, University of Sydney.

   This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.

Return to Gene Therapy Alert Section