title: 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.
abstract: OBJECTIVE
  Clinical 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Grewal
authors.affiliation: McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada; Department of Orthopaedics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Thornton
authors.affiliation: Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
authors.forename: Hayedeh
authors.initials: H
authors.lastname: Behzad
authors.affiliation: Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
authors.forename: Aishwariya
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Lu
authors.affiliation: Deptartment of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, Jack Bell Research Centre, Vancouver, BC, Canada.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Physical Therapy, University of Toronto, Toronto, ON, Canada.
authors.forename: W Darlene
authors.initials: WD
authors.lastname: Reid
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Centre for Hip Health and Mobility, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Granville Alex Scott
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D001696:Biomechanical Phenomena / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D013710:Tendons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; C439971:COL3A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D008077:Lipoproteins, LDL; D016212:Transforming Growth Factor beta; C099252:oxidized low density lipoprotein; D020778:Matrix Metalloproteinase 2