Impaired expression of genes regulating cholesterol efflux in human osteoarthritic chondrocytes.
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 (LXRalpha and LXRbeta) 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.
Tsezou
Aspasia
A
Department of Biology, Medical School, University of Thessaly, Mezourlo Hill, 41222 Larissa, Greece. atsezou@med.uth.gr
Iliopoulos
Dimitrios
D
Malizos
Konstantinos N
KN
Simopoulou
Theodora
T
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D050356:Lipid Metabolism / Q000235:genetics; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C577836:ABCA1 protein, human; C000605213:NR1H3 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides