Comparative analysis of gene expression in normal and degenerate human tendon cells : effects of cyclic strain

Abstract

Tendinopathy is a persistent clinical problem which has been treated with mixed results. Many of the limitations in the treatment of chronic painful tendinopathy are based on lack of knowledge of the molecular mechanisms of tissue regeneration. As the understanding of the key mediators of tissue regeneration and treatment effects develop, we believe that molecular gene expression signatures early in the mechanotransduction pathway will accurately predict risk stratification and correlate with different clinical outcomes. Studies aimed at elucidating the mechanism of tendinopathy have focused on small cohorts of genes which leave an incomplete picture of the tendon degeneration process. This study aimed to investigate tendinopathy via a comprehensive panel of mechanotransduction-related genes and cytoskeletal tensional homeostasis with and without the application of cyclic strain, which has been demonstrated to disrupt the normal homeostasis of connective tissue. Tendon samples of “normal” and “degenerate” portion were obtained from patients undergoing surgical procedures to treat chronic painful tendinopathy. A separate, but identical cyclic strain model was established in order to measure cytoskeletal tensional homeostasis. Before the cyclic strain, the normal tendon cells exhibited varying patterns of elevated expression of 7 genes compared with the degenerate tendon cells. In response to cyclic strain, cytoskeletal gene expression was up-regulated in normal tendon cells, especially in the expression of COL1A1, ITGA6, CTNNA1, and CLEC3B; however, cyclic strain had no effect on degenerate tendon cells. In addition, cyclic strain exacerbated the inhibition of protein expression in either type of cells, especially in the degenerate tendon cells. These data provide a more complete picture of tendinopathy, and a way to evaluate various promising treatments.