As phospho-OPN, both full-length and the C-terminal end, induce macrophage activation and thereby inflammation more than the dephosphorylated form of OPN, the high concentrations of phospho-OPN in RA synovial fluid and tissue under these circumstances may represent one possible pathogenic mechanism behind the chronic inflammatory disease or as is often observed in RA patients, the related bone destruction. This evidence concerns the gene SPP1 and rheumatoid arthritis.