IGF AND IGF-BINDING PROTEIN SYSTEM IN THE SYNOVIAL-FLUID OF OSTEOARTHRITIC AND RHEUMATOID ARTHRITIC PATIENTS

Various arthritic disorders result from a disruption of the equilibriu m between the synthesis and degradation of tissue matrix macromolecule s. Growth factors, particularly insulin-like growth factor-I (IGF-I), are believed to play an important role in maintaining this equilibrium . In this study, we determined the levels of IGF-I, IGF-II, and charac terized and measured the amount of IGF-binding proteins (IGFBPs) in th e synovial fluid (SF) of osteoarthritis (OA), rheumatoid arthritis (RA ) patients and normal individuals. Furthermore, we characterized the I GFBP found in these SFs. The levels of IGF-I, IGF-II and IGFBP-3 were determined by specific radioimmunoassays (RIAs). IGFBP identification and measurement were carried out using the Western ligand blot (WLB) t echnique, and characterization performed by Western immunoblot. IGFBP- 3 proteolysis was analyzed by autoradiography after incubation of SF w ith radiolabeled IGFBP-3. Results showed a statistically significant i ncrease (P < 0.001) in the IGF-I level in arthritic SF vs normal contr ols; 75 +/- 11 ng/ml and 82 +/- 11 ng/ml were recorded for RA (N = 8) and OA (N = 10), respectively, whilst normal controls (N = 9) were at 19 +/- 7 ng/ml. No difference in the level of IGF-II was recorded betw een the three groups studied. Human SF demonstrated the presence of IG FBP-1, -2, -3 and -4, but not that of IGFBP-5 and -6. The level of IGF BP-3 tested either by WLB or RIA was significantly higher (P < 0.001) in RA and OA patients. Moreover, a statistical and positive correlatio n between the levels of IGF-I and IGFBP-3 was noted. WLB analysis indi cated that the amount of IGFBP-1 did not vary among the groups. The le vels of IGFBP-2 and -4 were significantly increased (P < 0.02) solely in the RA SF. Further experiments demonstrated that a limited IGFBP-3 proteolysis occurred in human SF. Moreover, the ratio of total IGF ove r total bioactive IGFBPs was lower in RA (P < 0.05), and to a lesser e xtent in OA than normal specimens. This study showed the presence of f our IGFBPs (1-4) in human SF for which the IGFBP-2, -3 and -4 were enh anced in arthritic fluid. Importantly, although proteolysis occurred i n the SF, an increased amount of bioactive IGFBPs were present in arth ritic SF, which may affect the bioavailability of IGF-I within the art icular tissues.