In this study, we observed much higher S1P and VEGF expression in RA synovial fluid compared with OA samples, emphasizing the importance of S1P and VEGF in the pathogenesis of RA, which is reinforced by our evidence showing that S1P stimulates osteoblastic VEGF production and facilitates EPC angiogenesis by blocking miR-16-5p synthesis via c-Src/FAK signaling. Here, PTK2 is linked to rheumatoid arthritis.