Transforming growth factor-beta is a potent inhibitor of IL-1 induced protease activity and cartilage proteoglycan degradation

Biochem Biophys Res Commun. 1988 Dec 30;157(3):1352-9. doi: 10.1016/s0006-291x(88)81024-6.


Treatment of chondrocytes in culture with interleukin-1 results in the production of neutral proteases that cause the degradation of the large aggregating proteoglycan. TGF-beta is a pleiotropic growth factor that has been shown to induce differentiation of cartilage and, in some cases, was able to inhibit the IL-1-dependent processes. In this report, we examined whether TGF-beta could block the IL-1 induced catabolic effects on chondrocytes. After treatment with IL-1 beta (30 ng/ml), rabbit articular chondrocytes produced approximately 2 units of neutral protease activity. Under identical conditions, TGF-beta 1 alone did not induce any protease activity. However, a combination of IL-1 and TGF-beta resulted in a dramatic reduction in the level of protease activity. The inhibitory effect of TGF-beta was also observed at the level of proteoglycan incorporation into the extracellular matrix. The IL-1 treated chondrocytes failed to incorporate proteoglycans into their extracellular matrix. However, addition of TGF-beta in the presence of IL-1 resulted in partial reversal towards a normal extracellular matrix. These studies indicate that TGF-beta can block and at least partially inhibit the catabolic effects of IL-1 on chondrocytes.

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / enzymology*
  • Cells, Cultured
  • Chondroitin Lyases / metabolism
  • Chondroitin Sulfates / metabolism
  • Drug Synergism
  • Electrophoresis, Polyacrylamide Gel
  • Extracellular Matrix / metabolism
  • Fibroblast Growth Factors / pharmacology
  • Interleukin-1 / pharmacology*
  • Metalloendopeptidases / metabolism*
  • Proteoglycans / metabolism*
  • Rabbits
  • Recombinant Proteins / pharmacology
  • Sulfates / metabolism
  • Transforming Growth Factors / pharmacology*


  • Interleukin-1
  • Proteoglycans
  • Recombinant Proteins
  • Sulfates
  • Fibroblast Growth Factors
  • Transforming Growth Factors
  • Chondroitin Sulfates
  • Metalloendopeptidases
  • Chondroitin Lyases