Accumulation of oxidized LDL in the tendon tissues of C57BL/6 or apolipoprotein E knock-out mice that consume a high fat diet: potential impact on tendon health.

Navdeep Grewal,Alex Lu,Hayedeh Behzad,W Darlene Reid,Peng Zhang,Gail M Thornton,David J Granville,Alex Scott,Aishwariya Sharma,Hazel Rc Screen

doi:10.1371/journal.pone.0114214

Abstract

ObjectiveClinical studies have suggested an association between dyslipidemia and tendon injuries or chronic tendon pain; the mechanisms underlying this association are not yet known. The objectives of this study were (1) to evaluate the impact of a high fat diet on the function of load-bearing tendons and on the distribution in tendons of oxidized low density lipoprotein (oxLDL), and (2) to examine the effect of oxLDL on tendon fibroblast proliferation and gene expression.MethodsGene expression (Mmp2, Tgfb1, Col1a1, Col3a1), fat content (Oil Red O staining), oxLDL levels (immunohistochemistry) and tendon biomechanical properties were examined in mice (C57Bl/6 or ApoE -/-) receiving a standard or a high fat diet. Human tendon fibroblast proliferation and gene expression (COL1A1, COL3A1, MMP2) were examined following oxLDL exposure.ResultsIn both types of mice (C57Bl/6 or ApoE -/-), consumption of a high fat diet led to a marked increase in oxLDL deposition in the load-bearing extracellular matrix of the tendon. The consumption of a high fat diet also reduced the failure stress and load of the patellar tendon in both mouse types, and increased Mmp2 expression. ApoE -/- mice exhibited more pronounced reductions in tendon function than wild-type mice, and decreased expression of Col1a1 compared to wild type mice. Human tendon fibroblasts responded to oxLDL by increasing their proliferation and their mRNA levels of MMP2, while decreasing their mRNA levels for COL1A1 and COL3A1.ConclusionThe consumption of a high fat diet resulted in deleterious changes in tendon function, and these changes may be explained in part by the effects of oxLDL, which induced a proliferative, matrix-degrading phenotype in human tenocytes.

Highlights

Chronic tendinopathy is a widespread, age-related condition
There were no obvious differences among groups with regard to the macroscopic appearance of the tissue, with the exception of more peritendinous adipose tissue being observed in C57Bl/6 mice exposed to the high fat diet
There were no appreciable differences in the tendon morphology between mice on normal or high fat diet or between C57Bl/6 and ApoE -/- mice at any time point (0, 15 or 30 weeks)

Summary

Introduction

Much attention has been given to sport or occupation as risk factors, but there remains an unexplained association of tendinopathy and adiposity, both in active and sedentary populations [1]. Adiposity is associated with hyperlipidemia, a spectrum of plasma lipid abnormalities including elevated total cholesterol (TC), and elevated levels of low density lipoprotein (LDL-C). A previous study has shown that average TC and LDL-C were significantly higher in individuals who sustained an Achilles tendon injury compared to a control group, while high-density lipoprotein cholesterol concentration was significantly lower [3]. Abboud and Kim reported that rotator cuff tendinopathy patients demonstrate increased TC and LDL-C compared to controls [4]. Mechanisms linking high fat diet and tendon pathology have not been directly examined

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