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Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern

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Treatment with lipid-lowering drugs, statins, is common all over the world. Lately, the occurrence of spontaneous tendon ruptures or tendinosis have suggested a negative influence of statins upon tendon tissue. But how statins might influence tendons is not clear. In the present study, we investigated the effect of statin treatment on mechanical strength, cell proliferation, collagen content and gene expression pattern in a tendon-like tissue made from human tenocytes in vitro. Human tendon fibroblasts were grown in a 3D tissue culture model (tendon constructs), and treated with either simvastatin or atorvastatin, low or high dose, respectively, for up to seven days. After seven days of treatment, mechanical testing of the constructs was performed. Collagen content and cell proliferation were also determined. mRNA levels of several target genes were measured after one or seven days. The maximum force and stiffness were reduced by both statins after 7 days (p<0.05), while the cross sectional area was unaffected. Further, the collagen content was reduced by atorvastatin (p = 0.01) and the cell proliferation rate was decreased by both types of statins (p<0.05). Statin treatment also introduced increased mRNA levels of MMP-1, MMP-3, MMP-13, TIMP-1 and decreased levels of collagen type 1 and 3. In conclusion, statin treatment appears to have a negative effect on tendon matrix quality as seen by a reduced strength of the tendon constructs. Further, activated catabolic changes in the gene expression pattern and a reduced collagen content indicated a disturbed balance in matrix production of tendon due to statin administration.

Original languageEnglish
JournalP L o S One
Volume12
Issue number3
Pages (from-to)e0172797
ISSN1932-6203
DOIs
Publication statusPublished - 2017

    Research areas

  • Adolescent, Adult, Atorvastatin Calcium, Cell Proliferation, Cells, Cultured, Collagen, Energy Metabolism, Fibroblasts, Gene Expression Regulation, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Matrix Metalloproteinases, Mechanical Phenomena, Simvastatin, Tendon Injuries, Tendons, Tissue Inhibitor of Metalloproteinase-1, Young Adult, Journal Article

ID: 52387278