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

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

Author information

1
Department of Anatomy-Histology-Embryology, Unit of Bone and Soft Tissue Studies, University of Patras, School of Medicine, Patras, Greece.

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.

PMID:
23151457
DOI:
10.1016/j.joca.2012.11.003
[Indexed for MEDLINE]
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