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Enzymes aid invasion of arthritic joints

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Recent evidence suggests that enzymes which destroy cartilage aid invasive growth of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). An in vitro study has compared potential invasive properties of FLS from patients with RA, osteoarthritis (OA), and avascular necrosis (AVN) and found that FLS from RA had significantly more matrix metalloproteinases (MMPs).

Growth through an artificial matrix was greater for FLS from RA (median cell number 4788 v 1875 for OA, v 1530 for AVN), and so was growth rate (0.27 /day v 0.22 /day v 0.25 /day, respectively). However, growth rate showed no correlation with cell number.

FLS expressing MMP-1, MMP-3, or MMP-10 were significantly more invasive (median number of invasive cells 3835, 4248, and 4990, respectively) whether from RA or OA. But the odds of having MMP-1 and MMP-9 and RA were significant, 6.5 and 10.7, when compared with OA. Other attributes—expression of cathepsin-K and tissue inhibitors of MMP-1 and MMP-2—did not influence invasiveness.

FLS were cultured from tissue obtained from joint replacements or synovectomy in patients with RA (30), OA (17), and AVN (nine). Invasiveness was assayed in a Matrigel transwell culture system, by counting cells that migrated through the matrix after three days’ incubation. Growth rate was determined from cell counts of cultures harvested at intervals after seeding. Expression of cathepsin-K, tissue inhibitors, and MMPs was indicated by reverse transcriptase-PCR.

Activated FLS invade the synovium, articular cartilage, and bone in RA. Whether this is through increased growth or invasiveness has not been studied directly before now.

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