Characterization of TIMP-3 in human articular talar cartilage.
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.
Morris
Kirsten J
KJ
Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
Cs-Szabo
Gabriella
G
Cole
Ada A
AA
D000328:Adult; D002358:Cartilage, Articular / Q000166:cytology / Q000201:enzymology*; D019902:Chondrocytes / Q000201:enzymology; D005109:Extracellular Matrix / Q000201:enzymology; D006801:Humans; D013380:Subtalar Joint / Q000166:cytology / Q000201:enzymology*; D013628:Talus / Q000166:cytology / Q000201:enzymology*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3