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Comparative Analysis of Gene Expression in Normal and Degenerative Human Tendon Cells: Effects of Cyclic Strain

 Woo Jin Choi  ;  Min Sung Park  ;  Kwang Hwan Park  ;  Jean-Paul Courneya  ;  Jin Sun Cho  ;  Lew C. Schon  ;  Jin Woo Lee 
 FOOT & ANKLE INTERNATIONAL, Vol.35(10) : 1045-1056, 2014 
Journal Title
Issue Date
Adult ; Cell Proliferation ; Cells, Cultured ; Collagen Type I/genetics ; Collagen Type I/metabolism ; Female ; Gene Expression ; Humans ; Integrin alpha6/genetics ; Integrin alpha6/metabolism ; Lectins, C-Type/genetics ; Lectins, C-Type/metabolism ; Male ; Middle Aged ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Stress, Mechanical* ; Tendinopathy/genetics* ; Tendinopathy/pathology* ; Tendons/cytology* ; Up-Regulation ; alpha Catenin/genetics ; alpha Catenin/metabolism
cytoskeletal tensional balance ; mechanical strain ; superarray ; tendinopathy
BACKGROUND: Tendinopathy is a clinical problem for which treatment shows mixed results and treatment options are limited. Gene expression signatures early in the mechanotransduction pathway can accurately predict risk and correlate with different clinical outcomes. Studies aimed at elucidating the molecular mechanisms of tendinopathy have focused on small cohorts of genes that show an incomplete picture of the degeneration process. This study compared the effect of cyclic strain on gene expression in tendon cells from normal tendon and chronically painful areas of tendinopathy in 3 patients. METHODS: We measured a panel of mechanotransduction genes and cytoskeletal tensional balance with and without cyclic strain, which disrupts connective tissue synthetic-degradative equilibrium. Normal and degenerative tendons were obtained from patients undergoing surgery to treat chronic painful tendinopathy. A cyclic strain model was established to measure cytoskeletal tensional homeostasis. RESULTS: Prior to cyclic strain, the normal tendon cells exhibited varying patterns of elevated expression of 7 genes compared with degenerative tendon cells. In response to cyclic strain, gene expression of COL1A1, ITGA6, CTNNA1, and CLEC3B was up-regulated in normal tendon cells. Cyclic strain had no effect on degenerative tendon cells. Cyclic strain exacerbated the inhibition of protein synthesis in both cell types, especially in the degenerative tendon cells. CONCLUSION: Alterations in the pattern of gene expression are suggestive of a dynamic equilibrium between synthesis and degradation, whereby cell adhesion molecules are predominantly up-regulated to facilitate cellular reorientation in response to their altered functional environment. CLINICAL RELEVANCE: These data might have future applications, including the identification of markers for early diagnosis, targets for drug design, and indicators for treatment responsiveness and prognosis.
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1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Park, Kwang Hwan(박광환) ORCID logo https://orcid.org/0000-0002-2110-0559
Lee, Jin Woo(이진우) ORCID logo https://orcid.org/0000-0002-0293-9017
Cho, Jin Sun(조진선) ORCID logo https://orcid.org/0000-0002-5408-4188
Choi, Woo Jin(최우진)
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