Our results further indicate that a hypoxic and pro-inflammatory microenvironment induces the transcriptional activation of angiogenic growth factors in arthritic joints of CIA mice, including midkine and Hgf. Elevated levels of midkine have been detected in the serum and synovial fluid of RA patients [37,38], and HGF levels within the arthritic joint correlate with disease activity [39] and synovial microvessel density [13]. This evidence concerns the gene HGF and rheumatoid arthritis.