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.
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.
Shingleton
W D
WD
Department of Rheumatology, The Medical School, Unviersity of Newcastle upon Tyne, United Kingdom. W.D.Shingleton@ncl.ac.uk
Ellis
A J
AJ
Rowan
A D
AD
Cawston
T E
TE
D000818:Animals; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D004357:Drug Synergism; D007375:Interleukin-1 / Q000008:administration & dosage*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13; D010446:Peptide Fragments / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage*
D007375:Interleukin-1; D010446:Peptide Fragments; D011509:Proteoglycans; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014212:Tretinoin; D003094:Collagen; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1