title: Comparative analysis of gene expression in normal and degenerative human tendon cells: effects of cyclic strain.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea.
authors: Woo Jin
authors: WJ
authors: Choi
authors: Texas A&M Health Science Center College of Medicine, Institute for Regenerative Medicine, Temple, TX, USA.
authors: Min Sung
authors: MS
authors: Park
authors: Department of Pathology and Lab Medicine, Weill Cornell Medical College, New York, NY, USA.
authors: Kwang Hwan
authors: KH
authors: Park
authors: University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Jean-Paul
authors: JP
authors: Courneya
authors: Department of Anaesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: Jin Sun
authors: JS
authors: Cho
authors: Department of Orthopaedic Surgery, Union Memorial Hospital, Baltimore, MD, USA.
authors: Lew C
authors: LC
authors: Schon
authors: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea ljwos@yuhs.ac.
authors: Jin Woo
authors: JW
authors: Lee
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D015870:Gene Expression; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D052256:Tendinopathy / Q000235:genetics* / Q000473:pathology*; D013710:Tendons / Q000166:cytology*; D015854:Up-Regulation; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495273:CTNNA1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C588002:ITGA6 protein, human; D039503:Integrin alpha6; D037181:Lectins, C-Type; D012333:RNA, Messenger; D051178:alpha Catenin; C048648:tetranectin
keywords: cytoskeletal tensional balance; mechanical strain; superarray; tendinopathy