Functionally, Sema4B alone induced FLS migration and invasion, and enhanced the TNF-α or LPS-induced production of inflammatory mediators (Interleukin (IL)-6, IL-8, TNF-α, CCL-2) and matrix metalloproteases (MMP-1 and MMP-3) in RA FLS, RA MØ and the 3D synovium model. This evidence concerns the gene CCL2 and rheumatoid arthritis.