The recovery of articular cartilage in explant culture from interleukin-1 alpha: effects on proteoglycan synthesis and degradation.
The cytokine interleukin-1 (IL-1) strongly inhibits proteoglycan biosynthesis and increases extracellular proteoglycan degradation in cartilage. In this study we investigated how quickly proteoglycan turnover recovered after IL-1 treatment. Porcine articular cartilage in explant culture was incubated with recombinant human (rh) IL-1 alpha, rh insulin-like growth factor (IGF)-1 or rh-transforming growth factor (TGF)-beta 1 for 3 days. RhIL-1 alpha strongly inhibited synthesis and promoted matrix degradation over 3 days, whereas rhIGF-1 stimulated proteoglycan synthesis, and rhTGF-beta 1 had no significant effect on synthesis. In the absence of serum, the recovery of proteoglycan synthesis after IL-1 treatment (10 ng/ml) for 3 days was extremely slow, and it remained 30% inhibited even after a further 8 days of recovery. Matrix degradation of proteoglycan assessed from the rate of release of glycosaminoglycan into the culture medium recovered more quickly and was greatly reduced within 3 days. Shorter exposure of explants to IL-1 alpha (8 h) resulted in less inhibition of synthesis, but it did not result in a more rapid rate of recovery following its removal. Treatment of cartilage with IGF-1 (20 ng/ml) or TGF-beta (10 ng/ml) during the recovery period increased the rate of recovery of both synthesis and degradation. Synthesis recovered to control rates within 6 days and degradation within 2 days. TGF-beta (10 ng/ml) was slightly more potent than IGF-1. Fetal calf serum (10% v/v) also promoted recovery in a similar way to the growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Rayan
V
V
Biochemistry Division, Kennedy Institute, Hammersmith, London, UK.
Hardingham
T
T
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism*; D046508:Culture Techniques; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D011509:Proteoglycans / Q000096:biosynthesis* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I