Figure 10

Diagram summarizing major events in diosgenin-induced apoptosis in human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). The effect of diosgenin is associated with a loss of mitochondrial membrane potential (Δψm), caspase-3 activation, and DNA fragmentation. Furthermore, diosgenin causes an inhibition of human RA FLS cell growth with apoptosis induction associated with up-regulation of cyclooxygenase-2 (COX-2). Celecoxib, a selective COX-2 inhibitor, provokes a large decrease in diosgenin-induced apoptosis whereas IL-1β, a COX-2 inducer, strongly increases diosgenin-induced apoptosis of human RA FLS. These new studies provide strong evidence that modulation of COX-2 is associated with diosgenin-induced human RA FLS death. As exogenous prostaglandin E₂ (PGE₂) alone did not induce synoviocyte apoptosis, the exact mechanism by which endogenous PGE₂ sensitizes human RA FLS to cell death is still not clear.