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THU0052 Fibroblast-like synoviocytes from rheumatoid arthritis patients are more invasive than from osteoarthritis in an in vitro system: correlation with growth characteristics and expression of mmp-1, mmp-3 and mmp-10
  1. TC Tolboom1,
  2. E Pieterman1,
  3. WH Vd Laan2,
  4. AL Huidekoper1,
  5. RG Nelissen3,
  6. FC Breedveld1,
  7. TW Huizinga1
  1. 1Rheumatology
  2. 2Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands
  3. 3Orthopaedic Surgery

Abstract

Objectives Fibroblast-like synoviocytes (FLS) are involved in joint destruction. In this study the invasiveness in a transwell system in vitro was correlated with origin of synoviocytes. Moreover the relation between invasive growth of FLS in the transwell system and growth characteristics and expression of MMP 1-14, 17, 19, cathepsin K, TIMP-1 and -2 was determined.

Methods FLS were derived from 56 patients (30 rheumatoid arthritis (RA), 17 osteoarthritis (OA), 9 avascular necrosis (AVN) or fractures). Invasive growth of FLS through a collagen matrix was measured in a transwell system coated with matrigel. The number of cells grown through the matrix and the transwell membrane were counted. Growth rate was determined by counting of FLS after seven days of culturing. Expression of MMP’s, cathepsin-K and TIMP’s was investigated using RT-PCR and related to expression of a household gene, beta-actin.

Results FLS from RA invaded more easily in vitro than FLS from OA and AVN (median: RA: 4788 (cells grown through matrix and transwell membrane), OA: 1875; p <0.001 and AVN: 1530; p = 0.014 respectively). The median rate of proliferation of RA FLS was 0.27 per day compared to OA 0.22 per day (p = 0.012) and AVN and fractures 0.25 per day (RA versus AVN: p = 0.242; OA versus AVN: p = 0.553), but there was no correlation between rate of proliferation and invasive growth in vitro. FLS that expressed MMP-1, MMP-3 or MMP-10 were significantly more invasive (median number of invasive cells: 3835, 4248, 4990, respectively) than cells that did not express MMP-1, MMP-3 or MMP-10 (1605, p = 0.03; 1970, p = 0.004; 2360, p = 0.012, respectively). Expression of the other MMP’s, cathepsin-K and TIMP’s did not show a significant relationship with invasive growth. Expression of MMP-9 showed a trend with higher expression in more invasive cells (p = 0.066). There was also a significant relationship between the expression of MMP-1 and MMP-9 and a diagnosis of RA (both p = 0.013).

Conclusion FLS of RA invade more easily in a matrigel matrix than OA FLS. This is not due to a greater rate of proliferation of RA FLS than OA FLS, although FLS from RA patients have a 25% higher rate of proliferation than FLS from OA patients. A significant relationship exists between the expression of MMP-1, MMP-3 and MMP-10 and invisive growth in a matrigel transwell system and this relationship was nearly significant for MMP-9. FLS of RA patients expressed significantly more often MMP-1 and MMP-9 than FLS from OA patients.

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