Differential regulation of gene expression in isolated tendon fascicles exposed to cyclic tensile strain in vitro

Medical Engineering Division and Interdisciplinary Research Centre in Biomedical Materials, School of Engineering and Materials Science, Queen Mary, University of London, London, United Kingdom Submitted 29 July 2008 ; accepted in final form 25 November 2008 Mechanical stimulus is a regulator of tenocyte metabolism. The present study investigated temporal regulation of the expression of selected genes by tenocytes in isolated fascicles subjected to tensile strain in vitro. Cyclic tensile strain with a 3% amplitude superimposed on a 2% static strain was provided for 10 min, followed by either an unstrained period or continuous cyclic strain until the end of a 24-h incubation period. mRNA expression of selected anabolic and catabolic genes were evaluated with quantitative PCR at 10 min, 1 h, 6 h, and 24 h. The application of 6-h cyclic strain significantly upregulated type III collagen mRNA expression in strained fascicles compared with unstrained controls, but no alterations were observed in mRNA expression of type I collagen and biglycan . Significant downregulation in the expression of the decorin core protein was observed in fascicles subjected to 24-h cyclic strain. MMP3 and MMP13 expression levels were upregulated by the application of 10 min of cyclic strain, followed by a progressive downregulation until the end of the incubation period in both the absence and the presence of the continuing cyclic strain. Accordingly, alterations in the expression of anabolic genes were limited to the upregulation of type III collagen by prolonged exposure to cyclic strain, whereas catabolic genes were upregulated by a small number of strain cycles and downregulated by a prolonged cyclic strain. These findings demonstrate distinctive patterns of mechanoregulation for anabolic and catabolic genes and help our understanding of tenocyte response to mechanical stimulation. cyclic strain; metabolism; mechanobiology Address for reprint requests and other correspondence: D. A. Lee, Medical Engineering Div. and IRC in Biomedical Materials, School of Engineering and Materials Science, Queen Mary, Univ. of London, Mile End Rd., London, E1 4NS, UK (e-mail: d.a.lee{at}qmul.ac.uk )