Fibroblast-like synoviocytes obtained from different joints at different times from one patient show similar invasiveness in vitro

Background

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) have an aberrant behaviour. We have shown that FLSs from patients with RA display a different expression profile of matrix metalloproteinases, a different rate of proliferation and a different behaviour in an in vitro invasion model as compared with FLS from patients with osteoarthritis (OA) or fractures. Others have shown that FLSs in patients with RA show characteristics of transformation, such as an increased rate of proliferation, anchorage-independent growth and invasiveness in a SCID mouse invasion model. Interestingly, microdis-section studies recently showed that RA synovial tissue sections from different regions of the synovium were characterised by different p53 transition mutations, suggesting that oxidative stress leads to different mutations and can lead to different behaviour of FLSs. This observation suggests that even within a joint, the inflammatory stress can lead to differences in FLS behaviour.

Objective

We therefore wished to evaluate the differences between FLS populations obtained from different joints of the same patient, to gain a better understanding of the potential differences in invasive behaviour of FLSs within one patient. To do this, we analysed the invasiveness of FLSs obtained from different joints from one patient in an in vitro model.

Methods

Synovium was obtained from 11 patients (8 with RA and 3 with OA) at joint replacement surgery and FLSs were isolated from the tissue using enzymatic digestion. When the cells had grown to confluence, invasion was tested in transwells coated with Matrigel.

Results

The results show that the variation within one patient is smaller than the variation between patients (Fig. 1). These data suggest that the inflammatory process that drives the transition of synoviocytes to invasive FLSs is similar in different joints taken from the same patient.

Figure 1

Invasiveness of FLSs (in Matrigel) of two different joints from one patient.