title: Apolipoprotein-A1 as a damage-associated molecular patterns protein in osteoarthritis: ex vivo and in vitro pro-inflammatory properties.
abstract: Osteoarthritis (OA) is associated with a local inflammatory process. Dyslipidemia is known to be an underlying cause for the development of OA. Therefore, lipid and inflammatory levels were quantified ex vivo in blood and synovial fluid of OA patients (n=29) and compared to those of rheumatoid arthritis (RA) patients (n=27) or healthy volunteers (HV) (n=35). The role of apolipoprotein A-I (ApoA1) was investigated in vitro on inflammatory parameters using human joint cells isolated from cartilage and synovial membrane obtained from OA patients after joint replacement. Cells were stimulated with ApoA1 in the presence or not of serum amyloid A (SAA) protein and/or lipoproteins (LDL and HDL) at physiological concentration observed in OA synovial fluid. In our ex vivo study, ApoA1, LDL-C and total cholesterol levels were strongly correlated to each other inside the OA joint cavity whereas same levels were not or weakly correlated to their corresponding serum levels. In OA synovial fluid, ApoA1 was not as strongly correlated to HDL as observed in OA serum or in RA synovial fluid, suggesting a dissociative level between ApoA1 and HDL in OA synovial fluid. In vitro, ApoA1 induced IL-6, MMP-1 and MMP-3 expression by primary chondrocytes and fibroblast-like synoviocytes through TLR4 receptor. HDL and LDL attenuated joint inflammatory response induced by ApoA1 and SAA in a ratio dependent manner. In conclusion, a dysregulated lipidic profile in the synovial fluid of OA patients was observed and was correlated with inflammatory parameters in the OA joint cavity. Pro-inflammatory properties of ApoA1 were confirmed in vitro.
authors: Laboratory of Rheumatology, GIGA Research, University of Liege and CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Dominique
authors: D
authors: de Seny
authors: Laboratory of Rheumatology, GIGA Research, University of Liege and CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Gaël
authors: G
authors: Cobraiville
authors: Laboratory of Rheumatology, GIGA Research, University of Liege and CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Edith
authors: E
authors: Charlier
authors: Laboratory of Rheumatology, GIGA Research, University of Liege and CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Sophie
authors: S
authors: Neuville
authors: Laboratory of Clinical Chemistry, CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Laurence
authors: L
authors: Lutteri
authors: Laboratory of Clinical Chemistry, CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Caroline
authors: C
authors: Le Goff
authors: Laboratory of Rheumatology, GIGA Research, University of Liege and CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Denis
authors: D
authors: Malaise
authors: Laboratory of Rheumatology, GIGA Research, University of Liege and CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Olivier
authors: O
authors: Malaise
authors: Laboratory of Clinical Chemistry, CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Jean-Paul
authors: JP
authors: Chapelle
authors: Laboratory of Rheumatology, GIGA Research, University of Liege and CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Biserka
authors: B
authors: Relic
authors: Laboratory of Rheumatology, GIGA Research, University of Liege and CHU Hospital of Liege, 4000 Liège, Belgium.
authors: Michel G
authors: MG
authors: Malaise
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016632:Apolipoprotein A-I / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism*; D061251:Primary Cell Culture; D013582:Synovial Fluid / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015533:Transcriptional Activation; D055815:Young Adult
chemical_list: D016632:Apolipoprotein A-I; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1