Cholesterol secretion and homeostasis in chondrocytes: a liver X receptor and retinoid X receptor heterodimer mediates apolipoprotein A1 expression.
Cholesterol is required for chondrocyte differentiation and bone formation. Apolipoprotein A1 (apoA-1) plays a major role in lipoprotein clearance and cholesterol redistribution. We report here that apoA-1 is expressed during chondrocyte differentiation in vitro and in vivo. In differentiating chondrocytes, the expression of the liver X receptor (LXR) is modulated and its expression correlates to the expression of apoA-1. The expression of other LXR target genes related to cholesterol homeostasis such as ABCA1 cholesterol transporter and sterol regulatory element-binding protein 1 (SREBP1) is similarly regulated. Small molecule ligands activating either LXR or retinoid X receptor (RXR) lead to a dramatic increase in apoA-1 mRNA and protein expression in cultured chondrocytes. These ligands strongly induce ABCA1 cholesterol transporter expression and effectively mediate cholesterol efflux from hypertrophic chondrocytes. In addition, we report that, in the same cells, the ligands down modulate Serum Amyloid A expression induced by bacterial lipopolysaccharide. Our studies provide evidence that LXR/RXR mediate a fine regulation of cholesterol homeostasis in differentiating chondrocytes.
Gentili
C
C
Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Tutolo
G
G
Pianezzi
A
A
Cancedda
R
R
Descalzi Cancedda
F
F
D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry*; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002642:Chick Embryo; D002784:Cholesterol / Q000378:metabolism*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024121:Collagen Type X / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006706:Homeostasis; D047468:Immunoprecipitation; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D008074:Lipoproteins / Q000737:chemistry; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors / Q000737:chemistry / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000096:biosynthesis; D051780:Sterol Regulatory Element Binding Protein 1; D013696:Temperature; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
D016632:Apolipoprotein A-I; D022762:CCAAT-Enhancer-Binding Proteins; D024121:Collagen Type X; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D008074:Lipoproteins; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D047488:Retinoid X Receptors; D000685:Serum Amyloid A Protein; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D012313:RNA; D002784:Cholesterol