The effect of cyclical compressive loading on gene expression in articular cartilage.
Osteoarthritis (OA) develops as a consequence of articular cartilage degeneration possibly initiated by excessive or abnormal loading of the joint, and potentially mediated through a proteinase/proteinase inhibitor imbalance. We have shown previously that physiological loads (0.5 MPa, 1 Hz, 3 hour) elicit increased expression and activation of the matrix metalloproteinases (MMPs) in articular cartilage explants in vitro. The objective of this study was to identify mechanically-regulated genes involved in the observed induction of MMP expression and enhanced activation. Differential RNA Display (DRD) was used to identify mechanically-regulated genes by comparing DRD products derived from loaded and unloaded cartilage. One gene up-regulated in cartilage after 10, 30 and 60 minute loading revealed 83% homology with Mus musculus thymosin beta_4 which is known to induce MMP gene expression. The identification of mechanically regulated genes will greatly enhance our understanding of matrix turnover providing an exciting future in elucidating the role of mechanically-regulated genes in the development of OA.
Blain
Emma J
EJ
Connective Tissue Biology Laboratories, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, Wales, UK. BLAIN@cardiff.ac.uk
Mason
Deborah J
DJ
Duance
Victor C
VC
D000818:Animals; D001483:Base Sequence; D002358:Cartilage, Articular / Q000201:enzymology*; D002417:Cattle; D046508:Culture Techniques; D015971:Gene Expression Regulation, Enzymologic; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000201:enzymology / Q000235:genetics; D017385:Sequence Homology; D013314:Stress, Mechanical; D016474:Weight-Bearing
D020782:Matrix Metalloproteinases