Loading-induced changes in synovial fluid affect cartilage metabolism.
The object of this study was to determine whether changes in the synovial fluid (SF) induced by in vivo loading can alter the metabolic activity of chondrocytes in vitro, and, if so, whether insulin-like growth factor-I (IGF-I) is responsible for this effect. Therefore, SF was collected from ponies after a period of box rest and after they had been exercised for a week. Normal, unloaded articular cartilage explants were cultured in 20% solutions of these SFs for 4 days and chondrocyte bioactivity was determined by glycosaminoglycan (GAG) turnover (i.e., the incorporation of 35SO4 into GAG and the release of GAG into the medium). Furthermore, the extent to which the bioactivity is IGF-I-dependent was determined in a cartilage explant culture in 20% SF, in the presence and absence of anti-IGF-I antibodies. In explants cultured in post-exercise SF, GAG synthesis was enhanced and GAG release was diminished when compared to cultures in pre-exercise SF. SF analysis showed that IGF-I and IGFBP-3 levels were increased in post-exercise SF. There was a positive correlation between IGF-I levels and proteoglycan synthesis, but no correlation between IGF-I levels and proteoglycan release. Addition of anti-IGF-I antibodies significantly inhibited stimulation of proteoglycan synthesis in explants cultured in SF with 40%. However, there was no difference in inhibition of proteoglycan synthesis between pre- and post-exercise SF which indicated that the relative contribution of IGF-I in the stimulating effect of SF did not change. Proteoglycan release was not influenced by the presence of anti-IGF-I antibodies. It is concluded that chondrocyte metabolic activity is at least partially regulated by changes in the SF induced by in vivo loading. Exercise altered the SF in a way that it had a favourable effect on cartilage PG content by enhancing the PG synthesis and reducing the PG breakdown. IGF-I is an important contributor to the overall stimulating effect of SF on cartilage metabolism. It is, however, unlikely that IGF-I is the only mediator in the exercise-induced increase in this stimulating effect.
Faculty of Veterinary Sciences, Department of Biochemistry, Utrecht University, The Netherlands.
C H
CH
van de Lest
B M
BM
van den Hoogen
P R
PR
van Weeren
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D046508:Culture Techniques / Q000379:methods; D006025:Glycosaminoglycans / Q000378:metabolism; D006736:Horses; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000276:immunology; D008297:Male; D011509:Proteoglycans / Q000378:metabolism; D018709:Statistics, Nonparametric; D013314:Stress, Mechanical; D013582:Synovial Fluid / Q000502:physiology*
D000911:Antibodies, Monoclonal; D006025:Glycosaminoglycans; D018972:Insulin-Like Growth Factor Binding Protein 3; D011509:Proteoglycans; D007334:Insulin-Like Growth Factor I