Interphase fluorescence in situ hybridization analysis of fibroblast-like synoviocytes of patients with rheumatoid arthritis and osteoarthritis

Synovial stromal cells (e.g. fibroblast-like synoviocytes, FLS) are thought to play an essential role in the pathogenesis of inflammatory joint diseases, in particular in the destructive aspects of rheumatoid arthritis (RA). Recent evidence indicates that chromosomal alterations have a profound impact on cellular behavior, even in non-transformed cells. We therefore investigated whether or not alterations in chromosome number occur in FLS of patients with RA and osteoarthritis (OA).

Synovial tissue was collected at the time of joint surgery from 21 patients with RA and 22 patients with OA. Synoviocytes were isolated by enzymatic dispersion. Interphase fluorescence in situ hybridization (FISH) analysis of freshly isolated synoviocytes and stimulated or unstimulated cultured FLS was performed using DNA probes specific for chromosome 17, 8, 11, 6, 7 centromeres and the p53- (17p13), c-myc- (8q24), and the retinoblastome gene-1-(13q14) gene locus.

In all the patients studied, both RA and OA, concordant signal numbers with the probes recognizing chromosome 17, 8, 11 centromeres, 17p13, 8q24, and 13q14 were obtained (dual color FISH), indicating that allelic losses or gains of p53, c-myc, or the retinoblastoma gene-1 are not prevalent in fibroblast-like synoviocytes. Using α-satellite DNA probes specific for chromosome 6 or 7, alterations in chromosome number were identified in synoviocytes derived from some patients with both RA and OA.

In fibroblast-like synoviocytes, alterations in chromosome number and subsequent selection of chromosomally altered cells may occur in the joints of patients and contribute to the perpetuation of synovitis.