Thus, our results indicate that, despite their different etiologies and pathogenesis, both RA and OA are regulated by HIF-2α via completely different mechanisms: HIF-2α regulates OA pathogenesis by up-regulating matrix-degrading catabolic enzymes in articular chondrocytes, whereas it appears to regulate RA pathogenesis by regulating angiogenesis, various functions of FLS, and IL6-dependent TH17 cell differentiation. Here, IL6 is linked to rheumatoid arthritis.