In summary, HIF-2α is overexpressed in damaged chondrocytes as well as FLS in the pannus region in several experimental RA mouse models, and directly regulates the expression of Cxcl1, Cxcl2, Cxcl5, Cxcl10, and Ccl5. In addition, we have identified a previously unrecognized role of chondrocyte-derived chemokines and provided a mechanistic explanation for the regulatory processes underlying the invasive properties of FLS. This evidence concerns the gene CXCL2 and rheumatoid arthritis.