Up-regulation of matrix metalloproteinase expression and activation following cyclical compressive loading of articular cartilage in vitro.
Osteoarthritis (OA) results in articular cartilage degeneration and subchondral bone remodeling. Excessive or abnormal loading of the joint may contribute to matrix destruction by creating an imbalance between proteinases and their inhibitors. This study investigates whether cyclical loading regulates expression and/or activation of metalloproteinases 2 and 9 (MMPs) in articular cartilage explants. Gelatin zymography, reverse zymography, and MMP activity assays of mechanically loaded bovine cartilage explants (0.5 MPa, 1 Hz, 3 h) showed increased expression and activation of MMPs 2 and 9, whereas expression of the tissue inhibitors of MMPs was unaffected. This shows, for the first time that mechanical loading can influence tissue homeostasis generating an imbalance of proteinases and their inhibitors inducing turnover and/or catabolic events in cartilage.
Blain
E J
EJ
Connective Tissue Biology Laboratories, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, Wales, CF10 3US, United Kingdom. BLAIN@cardiff.ac.uk
Gilbert
S J
SJ
Wardale
R J
RJ
Capper
S J
SJ
Mason
D J
DJ
Duance
V C
VC
D000818:Animals; D002348:Carpal Bones / Q000502:physiology; D002358:Cartilage, Articular / Q000502:physiology*; D002417:Cattle; D015971:Gene Expression Regulation, Enzymologic; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008663:Metacarpus / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases / Q000032:analysis; D015854:Up-Regulation; D016474:Weight-Bearing
D019714:Tissue Inhibitor of Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9