Osteopontin May Play An Important Role In Rheumatoid Arthritis

Objective To explore the change of serum osteopontin(OPN) concentration in patients with rheumatoid arthritis(RA)and to study the relationships of the synovial expression of OPN and vascular endothelial growth factor(VEGF)with the degress of synovial angiogenesis in RA.Methods We measured the serum osteopontin concentration in 91 RA patients and 29 sex- and age-matched normal control subjects using an enzyme-linked immunoabsorbent assay and collected clinic date at the same time . Synovial tissue was obtained at synovectomy from seven patients with RA , five patients with osteoarthritis(OA) and 1 patient after external injury. Immunohischemistry was performed with anti-OPN and anti-VEGF antibodies. Ten high-power fields(hpf,40×) with clear cellularity at the level of the lining and sublining layers were evaluated for each patient. The number of positive cells and the number of vessels with an evident lumen were counted for each hpf. The final result was expressed as the number of positive cells or vessels/10hpf.Results①Serum osteopontin concentrations were significantly higher in RA patients with activity and RA patients with nonactivity than that in the normal control group. OPN in RA patients with activity(64.57±21.74) ng/ml; RA patients with nonactivity(55.97±21.86) ng/ml; normal subjects (25.97±8.28) ng/ml , (P<0.005). OPN concentration correlated positively and significantly with the joint numbers of tenderness , joint x-ray stages, joint function(r=0.435,P=0.005, r=0.415,P=0.007,r=0.394,P=0.012).②OPN was detected in the synovial lining and sublining layers with RA and OA. In contrast, althought the external injury patient synovium also showed some OPN straining, the expression was less notable and was scatted. OPN was strained in kytoplasm .The number of positive OPN cells in lining and sublining layer with RA was significantly higher than that in the same area of OA(P=0.048,P=0.030). The number of positive OPN cells in sublining layer was more than the lining layer in RA(P=0.018)It was absent in lymphoid aggregates. All synovial specimens showed OPN intense expression in vascular endothelial cell and vascular smooth muscle cell. OPN was also present in cartilage and strained in kytoplasm and nucleus. OPN expression in lining and sublining layer correlated with the number of vessels present in the the sublining laye(rr=0.837 P=0.019;r=0.946 P=0.001).No signification correlation was found between OPN and vessels in OA.③VEGF was abundantly expressed in both lining and the sublining layer synovium. The number of positive VEGF cells in sublining layer was more than the lining layer in RA(P=0.028).The VEGF positive number between lining and sublining did not achieve statistical significance(P=0.138).In RA ,VEGF expression in sublining layer correlated with the number of vessels present in the same layer(r=0.982 P=0.010).④In RA ,OPN expression in lining and sublining layer correlated with the VEGF expression in the the lining and sublining layer(r=0.821 P=0.023;r=0.964 P=0.01). In OA, there is no correlation between OPN and VEGF.Conclusions The above results suggest that the production of OPN is associated with the activity of disease and the destruction of joint in RA. OPN expression was correlated with the VEGF expression in the the lining and sublining layer .OPN is very important in angiogenesis with RA. OPN and VEGF may participate in the forming of synovial pannus and the destroy of cartilage with synergism.