Recently, we have identified the overexpression of Shh signaling in RA synovium and selective inhibition of Shh by blocking Smo suppressed the proliferation of RA-FLSs, accompanying with the decreased expression of Gli1 in FLSs isolated from RA synovium (RA-FLSs) (12, 13). This evidence concerns the gene SHH and rheumatoid arthritis.