Characterization of TIMP-3 in human articular talar cartilage

Connect Tissue Res. 2010 Dec;51(6):478-90. doi: 10.3109/03008201003686958. Epub 2010 Apr 13.


Tissue inhibitor of matrix metalloproteinase 3 (TIMP-3) is an inhibitor of matrix degradation; however, little else is known about the role(s) of this protein in articular cartilage. In this study we compared levels of TIMP-3 in human knee and ankle cartilages and in normal and degraded cartilages. In addition, our studies focused on the compartmentalization of TIMP-3 in human adult articular cartilage matrix, identification of its potential binding partners, and determining the effects of cytokines on its matrix compartment deposition. We extracted TIMP-3 from cartilage and found that while TIMP-3 was localized throughout the matrix, it was predominately associated with the chondrocyte. We also found that more TIMP-3 was extracted from normal compared to degraded cartilage and more in ankle than knee cartilage suggesting the potential of this inhibitor as a protective agent. Our data suggest that TIMP-3 interacts with heparan sulfate and heparan sulfate proteoglycans and to a lesser extent with heparin and chondroitin sulfate. Stimulation with Interleukin-1β and osteogenic protein-1 decreased while tumor necrosis factor alpha and transforming growth factor beta increased TIMP-3 protein levels; however, TIMP-3 mRNA was not significantly affected by any of these treatments. These characteristics indicate the chondroprotective nature of TIMP-3 and its potential as a therapeutic agent for osteoarthritis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cartilage, Articular / cytology
  • Cartilage, Articular / enzymology*
  • Chondrocytes / enzymology
  • Extracellular Matrix / enzymology
  • Humans
  • Subtalar Joint / cytology
  • Subtalar Joint / enzymology*
  • Talus / cytology
  • Talus / enzymology*
  • Tissue Inhibitor of Metalloproteinase-3 / chemistry*
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism


  • TIMP3 protein, human
  • Tissue Inhibitor of Metalloproteinase-3