THE STIMULATION OF MONONUCLEAR-CELLS FROM PATIENTS WITH RHEUMATOID-ARTHRITIS TO DEGRADE ARTICULAR-CARTILAGE IS NOT MODULATED BY CARTILAGE ITSELF

Objective. To study the modulation of mononuclear cell (MNC) activity in patients with rheumatoid arthritis (RA) by constituents released fr om human articular cartilage, which may be present in vivo during earl y events of the disease, when articular cartilage is not or is only mi ldly damaged. Methods. In an attempt to stimulate RA MNC, cells were c o-cultured with healthy or mildly damaged articular cartilage tissue. In addition, because of the reported cross-reactivity between cartilag e constituents and mycobacterial heat-shock protein (hsp60), RA MNC se nsitized with hsp60 were also co-cultured with cartilage tissue. Activ ation of the RA MNC was assessed by analysing the production of catabo lic factors involved in joint damage. For this purpose culture superna tants of the treated R4 MNC, comprising the catabolic factors, were ad ded to freshly isolated articular cartilage explants. As a read out fo r catabolic activity, proteoglycan (PG) turnover by the explants was d etermined. Results. Spontaneous activity of untreated RA MNC caused in hibition of PG synthesis and increased PG release upon addition of the ir culture supernatants to the cartilage explants. This MNC activity w as not enhanced by the constituents released fro, healthy or mildly da maged cartilage tissue, whereas sensitization of RA MNC with hsp60 res ulted in a 40% enhanced inhibition of PG synthesis. However, even unde r these pre-activated conditions no reactivity towards the cartilage c onstituents could be observed. Conclusion. Cartilage constituents rele ased from mildly damaged cartilage tissue, as may be present during th e early events of RA. do not modulate the catabolic activity of RA MNC .