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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
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Bispebjerg Hospital, Denmark; University of Copenhagen, Denmark.
Bispebjerg Hospital, Denmark; University of Copenhagen, Denmark.
Bispebjerg Hospital, Denmark; University of Copenhagen, Denmark.
Bispebjerg Hospital, Denmark; University of Copenhagen, Denmark.
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, e0172797Article in journal (Refereed) Published
Abstract [en]

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 (pamp;lt;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 (pamp;lt;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.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE , 2017. Vol. 12, no 3, e0172797
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-136042DOI: 10.1371/journal.pone.0172797ISI: 000396054300018PubMedID: 28264197OAI: oai:DiVA.org:liu-136042DiVA: diva2:1084885
Note

Funding Agencies|Lundbeck Foundation; Nordea Foundation; IOC Sports medicine Copenhagen; Danish Medical Research Council [0602-02960B]; Swedish Society for Medical Research; Magnus Bergyall Foundation; Lions research foundation

Available from: 2017-03-27 Created: 2017-03-27 Last updated: 2017-04-14

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