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<div><p>Osteoarthritis (OA) is a joint disease in which cartilage degradation is the hallmark pathological change. In this study, we investigated the anti-osteoarthritic effects of DHEA in rabbit chondrocytes. Polymerase chain reaction was performed to evaluate the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, aggrecan and collagen type 2. In addition, ERK1/2 signaling pathway components were analyzed by Western blotting. In IL-1β-induced chondrocytes, the phosphorylation of ERK1/2 was enhanced, and the downstream catabolic genes, including ADAMTS-4 and ADAMTS-5, were upregulated, while the anabolic genes aggrecan and collagen type 2 were downregulated. DHEA administration restored the IL-1β-induced imbalance in anabolic and catabolic gene expression. In addition, the phosphorylation of ERK1/2 was suppressed by DHEA. Then, PD98059 was used to block the ERK1/2 signaling pathway. The protective effect of DHEA was significantly increased when ERK1/2 signaling was inactivated. DHEA may exert its protective effect by suppressing ADAMTS in an ERK1/2-dependent manner in rabbit chondrocytes.</p></div>