title: Perturbations in the HDL metabolic pathway predispose to the development of osteoarthritis in mice following long-term exposure to western-type diet.
abstract: OBJECTIVE
  Recent data suggest that obesity and related metabolic aberrations are associated with osteoarthritis (OA) development, a phenomenon that is attributed at least in part to the consumption of lipid-rich diets. To date, the molecular mechanisms that govern the lipid-OA connection remain largely unknown. Given the important role of high-density lipoprotein (HDL) in plasma and tissue lipid metabolism, the main purpose of the present study was to investigate the role of HDL metabolism in the pathobiology of OA.
  
  
  METHODS
  We used apolipoprotein A-I (apoA-I)(-/-) mice that lack classical apoA-I containing HDL, LCAT(-/-) mice that have only immature HDL and relatively reduced HDL-cholesterol levels and control C57BL/6 mice. Mice were placed on chow or western-type (WTD) and monitored for 24 weeks. Knee joints were removed and articular cartilage was isolated for further analyses.
  
  
  RESULTS
  The LCAT(-/-) mice were significantly more sensitive to the development of diet-induced obesity compared to the C57BL/6 and apoA-I(-/-) mice. Morphological, biochemical and molecular analyses revealed that the LCAT(-/-) obese mice developed OA, while the C57BL/6 mice that were fed WTD did not. Notably, apoA-I(-/-) mice that received WTD also developed OA although their body-weight gain was similar to their wild-type counterparts. Interestingly, bone marrow from LCAT(-/-) and apoA-I(-/-) mice contained significantly increased number of adipocytes, compared to the other groups.
  
  
  CONCLUSIONS
  Our findings suggest that perturbations in HDL metabolism predispose to OA following chronic insult with WTD and raise the challenging possibility that HDL has a causative relation to OA in patients with metabolic syndrome.
authors.affiliation: Department of Anatomy-Histology-Embryology, Unit of Bone and Soft Tissue Studies, University of Patras, School of Medicine, Patras, Greece.
authors.forename: I-E
authors.initials: IE
authors.lastname: Triantaphyllidou
authors.forename: E
authors.initials: E
authors.lastname: Kalyvioti
authors.forename: E
authors.initials: E
authors.lastname: Karavia
authors.forename: I
authors.initials: I
authors.lastname: Lilis
authors.forename: K E
authors.initials: KE
authors.lastname: Kypreos
authors.forename: D J
authors.initials: DJ
authors.lastname: Papachristou
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D015984:Causality; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000378:metabolism / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000503:physiopathology*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D019366:Western World
chemical_list: D016632:Apolipoprotein A-I; D008055:Lipids; D008075:Lipoproteins, HDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase