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The invasiveness of fibroblast-like synoviocytes is of relevance for the rate of joint destruction in patients with rheumatoid arthritis and is a patient characteristic

  • TCA Tolboom1,
  • AHM van der Helm-van Mil1,
  • RGHH Nelissen2,
  • FC Breedveld1,
  • REM Toes1 and
  • TWJ Huizinga1
Arthritis Research & Therapy20057(Suppl 1):P42

Received: 11 January 2005

Published: 17 February 2005


Rheumatoid ArthritisDisease DurationSynovial TissueSCID MouseJoint Destruction


Rheumatoid arthritis (RA) is characterized by inflammation of synovial joints and degradation of these joints. Fibroblast-like synoviocytes (FLS) are thought to play a role, because they can invade normal human cartilage in SCID mice [1] and matrigel in vitro [2]. This study was undertaken to investigate the association of these in vitro characteristics with the disease characteristics in patients with RA.


Synovial tissue samples of 72 RA and 50 osteoarthritis patients were obtained; from seven patients with RA, samples of different joints were collected. The FLS invasiveness in Matrigel matrix was studied; the intra-individual and inter-individual differences were compared. The radiological scores of the X-rays of the hands and feet of the patients with the FLS that exhibit the most extreme differences in in vitro ingrowth (most invasive and least invasive FLS) were determined with the Sharp–van der Heijde method to determine the relationship between in vitro invasion data and clinical data.


FLS from patients with RA are more invasive than FLS from patients with osteoarthritis (P < 0.001). The intra-individual variation in FLS invasion was much less than the inter-individual variation (P = 0.028; mean difference ± standard deviation, 1204 ± 926 and 3476 ± 2367 for intra-individual and inter-individual variation, respectively), showing that the level of FLS invasion is a patient characteristic. The mean Sharp score of X-rays of the hands and feet divided by the disease duration was 4.7 ± 3.2 units per year of disease duration (n = 9) for the patients with the least invasive disease, which was much lower as compared with 22.3 ± 9.4 units per year of disease duration (n = 8) for the patients with the most invasive disease (P < 0.001).


The ex vivo behaviour of FLS is a patient characteristic given the small intra-individual variation, and is highly correlated with the rate of joint destruction in patients with RA. This suggests that the ex vivo invasive behaviour of FLS from patients with RA is of relevance for the rate of joint destruction in patients with RA.



TCAT and AHMvdH-vM contributed equally to this work.

Authors’ Affiliations

Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
Department of Orthopedics, Leiden University Medical Center, Leiden, The Netherlands


  1. Muller-Ladner U, Kriegsmann J, Franklin BN, Matsumoto S, Geiler T, Gay RE, Gay S: Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am J Pathol. 1996, 149: 1607-1615.PubMed CentralPubMedGoogle Scholar
  2. Tolboom TC, Pieterman E, Van Der Laan WH, Toes RE, Huidekoper AL, Nelissen RG, Breedveld FC, Huizinga TW: Invasive properties of fibroblast-like synoviocytes: correlation with growth characteristics and expression of MMP-1, MMP-3, and MMP-10. Ann Rheum Dis. 2002, 61: 975-980. 10.1136/ard.61.11.975.PubMed CentralView ArticlePubMedGoogle Scholar


© BioMed Central Ltd 2005