Osteoarthritis is a multi-factorial disease process driven by the master regulators of cellular/ECM destruction, IL-1β and TNFα, pro-inflammatory molecules such as the COX-2-dependent cartilage-destructive enzyme prostaglandin E2 (PGE2), IL-6, IL-8, and the ECM-degrading enzymes such as the MMPs. The gene discussed is TNF; the disease is osteoarthritis.