One of the first studies where OPN was associated with RA pathology was carried out by Petrow and colleagues, where they demonstrated that FLS produced OPN at the sites of cartilage invasion and in the synovial lining layer, inducing the attachment of FLS to the cartilage and producing MMP-1 in chondrocytes that contributes to ECM degradation [131]. The gene discussed is SPP1; the disease is rheumatoid arthritis.