Impaired Expression of Genes Regulating Cholesterol Efflux in Human Osteoarthritic Chondrocytes

Abstract

Altered lipid metabolism has been implicated as a critical player in osteoarthritis (OA). Our study aimed to investigate the expression of genes regulating cholesterol efflux in human chondrocytes and to study the effect of an LXR agonist on cholesterol efflux and lipid accumulation in osteoarthritic chondrocytes. ATP-binding-cassette transporter A1 (ABCA1), apolipoprotein A1 (ApoA1), and liver X receptors (LXR alpha and LXR beta) mRNA expression levels were evaluated using real-time polymerase chain reaction (PCR) and ApoA1 protein levels by Western blot analysis in normal and osteoarthritic articular cartilage samples. Cholesterol efflux was evaluated in osteoarthritic chondrocytes radiolabeled with [1,2(n)-(3)H] cholesterol after LXR treatment, while intracellular lipid accumulation was studied after Oil-red-O staining. Cholesterol efflux gene expressions were significantly lower in osteoarthritic cartilage compared to normal. Treatment of osteoarthritic chondrocytes with the LXR agonist TO-901317 significantly increased ApoA1 and ABCA1 expression levels, as well as cholesterol efflux. Additionally, osteoarthritic chondrocytes presented intracellular lipids deposits, while no deposits were found after treatment with TO-901317. Our findings suggest that impaired expression of genes regulating cholesterol efflux may be a critical player in osteoarthritis, while the ability of the LXR agonist to facilitate cholesterol efflux suggests that it may be a target for therapeutic intervention in osteoarthritis. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1033-1039, 2010