title: Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli.
abstract: While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ).
  
  
  
  The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay.
  
  
  
  We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli.
  
  
  
  The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses.
authors.affiliation: INSERM UMR-S1109, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Ghada
authors.initials: G
authors.lastname: Alsaleh
authors.affiliation: INSERM UMR-S1109, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Nehmar
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Blüml
authors.affiliation: INSERM UMR-S1109, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Schleiss
authors.affiliation: INSERM UMR-S1109, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Ostermann
authors.affiliation: Hôpitaux Universitaires de Strasbourg and CNRS, Université de Strasbourg, Strasbourg, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Dillenseger
authors.affiliation: CNRS, Université de Strasbourg, Strasbourg, France.
authors.forename: Amira
authors.initials: A
authors.lastname: Sayeh
authors.affiliation: Hôpitaux Universitaires de Strasbourg and CNRS, Université de Strasbourg, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Choquet
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U964, CNRS UMR-7104, and Université de Strasbourg, Illkirch, France.
authors.forename: Doulaye
authors.initials: D
authors.lastname: Dembele
authors.affiliation: INSERM UMR-S1109, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Francois
authors.affiliation: Centre Hospitalier Universitaire de Reims, Reims, France.
authors.forename: Jean-Hugues
authors.initials: JH
authors.lastname: Salmon
authors.affiliation: INSERM UMR-S1109, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Nicodème
authors.initials: N
authors.lastname: Paul
authors.affiliation: Institute for Physiology, Center for Physiology and Pharmacology, and Medical University of Vienna, Vienna, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Schabbauer
authors.affiliation: Hôpitaux Universitaires de Strasbourg and Université de Strasbourg, Strasbourg, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bierry
authors.affiliation: Hôpital de Hautepierre, Centre de Référence des Maladies Auto-immunes Rares, and Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Meyer
authors.affiliation: INSERM UMR-S1109, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.affiliation: Architecture et Réactivité de l'ARN, UPR-9002, and Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Haas
authors.affiliation: Architecture et Réactivité de l'ARN, UPR-9002, and Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Pfeffer
authors.affiliation: INSERM UMR-S1109, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Vallat
authors.affiliation: Hôpital de Hautepierre, Centre de Référence des Maladies Auto-immunes Rares, Hôpitaux Universitaires de Strasbourg, and INSERM UMR-S1109, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.affiliation: INSERM UMR-S1109, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Seiamak
authors.initials: S
authors.lastname: Bahram
authors.affiliation: INSERM UMR-S1109, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche en Immunologie et Hématologie, and Université de Strasbourg, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Georgel
mesh_terms: D000818:Animals; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D051379:Mice; D043244:Ribonuclease III / Q000235:genetics*; D000070918:Synoviocytes / Q000502:physiology*
chemical_list: C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases