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

MedStar author(s):
Citation: Foot & Ankle International. 35(10):1045-56, 2014 Oct.Foot Ankle Int. 35(10):1045-56, 2014 Oct.PMID: 24958764Institution: MedStar Union Memorial HospitalDepartment: Orthopaedic SurgeryForm of publication: Journal ArticleMedline article type(s): Comparative Study | Journal Article | Research Support, Non-U.S. Gov'tSubject headings: *Stress, Mechanical | *Tendinopathy/ge [Genetics] | *Tendinopathy/pa [Pathology] | *Tendons/cy [Cytology] | Adult | alpha Catenin/ge [Genetics] | alpha Catenin/me [Metabolism] | Cell Proliferation | Cells, Cultured | Collagen Type I/ge [Genetics] | Collagen Type I/me [Metabolism] | Female | Gene Expression | Humans | Integrin alpha6/ge [Genetics] | Integrin alpha6/me [Metabolism] | Lectins, C-Type/ge [Genetics] | Lectins, C-Type/me [Metabolism] | Male | Middle Aged | RNA, Messenger/ge [Genetics] | RNA, Messenger/me [Metabolism] | Up-RegulationYear: 2014Local holdings: Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2006ISSN:
  • 1071-1007
Name of journal: Foot & ankle internationalAbstract: 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.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.Copyright © The Author(s) 2014.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.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.All authors: Cho JS, Choi WJ, Courneya JP, Lee JW, Park KH, Park MS, Schon LCFiscal year: FY2015Digital Object Identifier: Date added to catalog: 2016-07-15
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 24958764 Available 24958764

Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2006

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.

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.Copyright © The Author(s) 2014.

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.

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.

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