Local disruption of the insulin-like growth factor system in the arthritic joint.

Abstract

To identify differences in levels of insulin-like growth factor (IGF) and IGF binding proteins (IG-FBPs) between 30 patients with arthritis (14 with rheumatoid arthritis [RA], 16 with osteoarthritis [OA]) and 11 normal control subjects. IGF and IGFBP levels were correlated to the disease activity marker C-reactive protein (CRP) to determine whether they were disease related. We also examined the degree of proteolytic modification of the IGFBPs. Radioimmunoassays were used for measuring IGF and IGFBP-3 levels; CRP was measured by enzyme-linked immunosorbent assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting, chemiluminescence, and autoradiography were used for visualizing binding proteins. There was a significant increase in synovial fluid levels of both IGF-1 and IGFBP-3 in both RA and OA. This resulted in an elevated IGFBP-3 to IGF molar ratio of 1.49 in the OA group and 1.47 in the RA group, compared with 0.86 in the normal control group (P = 0.0002 for both). A significantly lower degree of IGFBP-3 proteolysis was also seen in the synovial fluids from the patients compared with the controls. There were significant correlations between the CRP level and levels of IGF-1, IGF-2, and IGFBP-3 in the RA patients (r = 0.62-0.898, P = 0.04-0.0007). There was significant local disruption of the IGF system in patients with arthritis. This may result in a lower amount of IGF that is able to bind to IGF receptors in the arthritic joint. Levels of IGF-1 IGF-2, and IGFBP-3 all correlated with the CRP level in patients with RA, which indicates the possibility that the IGF system is involved in the disease process.