To study the modulation of mononuclear cell (MNC) activity in patients with rheumatoid arthritis (RA) by constituents released from human articular cartilage, which may be present in vivo during early events of the disease, when articular cartilage is not only mildly damaged.
In an attempt to stimulate RA MNC, cells were co-cultured with healthy or mildly damaged articular cartilage tissue. In addition, because of the reported cross-reactivity between cartilage constituents and mycobacterial heat-shock protein (hsp60), RA MNC sensitized with hsp60 were also co-cultured with cartilage tissue. Activation of the RA MNC was assessed by analysing the production of catabolic factors involved in joint damage. For this purpose culture supernatants of the treated RA MNC, comprising the catabolic factors, were added to freshly isolated articular cartilage explants. As a read out for catabolic activity, proteoglycan (PG) turnover by the explants was determined.
Spontaneous activity of untreated RA MNC caused inhibition of PG synthesis and increased PG release upon addition of their culture supernatants to the cartilage explants. This MNC activity was not enhanced by the constituents released from healthy or mildly damaged cartilage tissue, whereas sensitization of RA MNC with hsp60 resulted in a 40% enhanced inhibition of PG synthesis. However, even under these pre-activated conditions no reactivity towards the cartilage constituents could be observed.
Cartilage constituents released from mildly damaged cartilage tissue, as may be present during the early events of RA. do not modulate the catabolic activity of RA MNC.