Perturbations in the HDL metabolic pathway predispose to the development of osteoarthritis in mice following long-term exposure to western-type diet

Osteoarthritis Cartilage. 2013 Feb;21(2):322-30. doi: 10.1016/j.joca.2012.11.003. Epub 2012 Nov 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein A-I / deficiency
  • Apolipoprotein A-I / genetics
  • Apolipoprotein A-I / metabolism
  • Body Weight / physiology
  • Causality
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Lecithin Cholesterol Acyltransferase Deficiency / metabolism
  • Lecithin Cholesterol Acyltransferase Deficiency / physiopathology
  • Lipids / blood
  • Lipoproteins, HDL / metabolism*
  • Male
  • Metabolic Networks and Pathways / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / etiology
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Osteoarthritis, Knee / metabolism*
  • Osteoarthritis, Knee / physiopathology*
  • Phosphatidylcholine-Sterol O-Acyltransferase / genetics
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism
  • Time Factors
  • Western World


  • Apolipoprotein A-I
  • Lipids
  • Lipoproteins, HDL
  • Phosphatidylcholine-Sterol O-Acyltransferase