N. Grewal, G. Thornton, H. Behzad, A. Sharma, A. Lu, P. Zhang, D. Reid, D. Granville, A. Scott
PLOS ONE, 9(12), e114214, (2014)
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.
Gene 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.
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.
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.