Retinoic acid combines with interleukin-1 to promote the degradation of collagen from bovine nasal cartilage: matrix metalloproteinases-1 and -13 are involved in cartilage collagen breakdown

J Cell Biochem. 2000 Sep 14;79(4):519-31.


Retinoic acid (RetA) and interleukin-1alpha (IL-1) together can induce a reproducible release of proteoglycan fragments from bovine nasal cartilage in culture. However, release of collagen fragments with either agent alone is often variable. In this study over 70% of the total collagen was released from bovine nasal cartilage in culture by day 14 when RetA and IL-1 were combined. This release was accompanied by the appearance of collagenolytic activity in the culture medium that cleaved collagen specifically at the (1/4)/(3/4) position. Tissue inhibitor of metalloproteinases (TIMP) activity was present at day 7 but low or absent in media from resorbing tissue at day 14. The breakdown of cartilage collagen could be prevented by the addition of BB-94, a specific metalloproteinase inhibitor. These results suggest that RetA promotes the early release of TIMP from the tissue and that IL-1 stimulates pro-collagenase secretion which, when activated, exceeds the local concentration of TIMP. Thus in the later stages of culture collagen destruction occurs. Both MMP-1 and MMP-13 were detected and appear to be involved in IL-1 + RetA induced bovine cartilage destruction. However, for the first time, we also present evidence to suggest that MMP-13 is the predominant collagenase in this system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage / drug effects*
  • Cartilage / metabolism*
  • Cattle
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Collagen / metabolism*
  • Collagenases / genetics
  • Collagenases / metabolism*
  • Drug Synergism
  • Interleukin-1 / administration & dosage*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 13
  • Peptide Fragments / metabolism
  • Proteoglycans / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tretinoin / administration & dosage*


  • Interleukin-1
  • Peptide Fragments
  • Proteoglycans
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Tretinoin
  • Collagen
  • Collagenases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 1