k) HIF-2α: HIF-2α is also upregulated in chondrocytes of RA [67] and when co-cultured with HIF-2α-overexpressing chondrocytes, synovial fibroblasts show increased expression of matrix degradation enzymes (MMP3, MMP9, MMP12, MMP13) and various inflammatory mediators [68] and enhanced migration and invasion, while conditional knockout of HIF-2α in cartilage tissue inhibits pannus formation in adjacent cartilage [69]. This evidence concerns the gene EPAS1 and rheumatoid arthritis.