title: The pro-inflammatory cytokine 14-3-3ε is a ligand of CD13 in cartilage.
abstract: Osteoarthritis is a whole-joint disease characterized by the progressive destruction of articular cartilage involving abnormal communication between subchondral bone and cartilage. Our team previously identified 14-3-3ε protein as a subchondral bone soluble mediator altering cartilage homeostasis. The aim of this study was to investigate the involvement of CD13 (also known as aminopeptidase N, APN) in the chondrocyte response to 14-3-3ε. After identifying CD13 in chondrocytes, we knocked down CD13 with small interfering RNA (siRNA) and blocking antibodies in articular chondrocytes. 14-3-3ε-induced MMP-3 and MMP-13 was significantly reduced with CD13 knockdown, which suggests that it has a crucial role in 14-3-3ε signal transduction. Aminopeptidase N activity was identified in chondrocytes, but the activity was unchanged after stimulation with 14-3-3ε. Direct interaction between CD13 and 14-3-3ε was then demonstrated by surface plasmon resonance. Using labeled 14-3-3ε, we also found that 14-3-3ε binds to the surface of chondrocytes in a manner that is dependent on CD13. Taken together, these results suggest that 14-3-3ε might directly bind to CD13, which transmits its signal in chondrocytes to induce a catabolic phenotype similar to that observed in osteoarthritis. The 14-3-3ε-CD13 interaction could be a new therapeutic target in osteoarthritis.
authors.affiliation: UMR_S938, CDR Saint-Antoine - INSERM - University Pierre & Marie Curie Paris VI, Sorbonne Universités, 7 quai St-Bernard, Paris 75252, Cedex 5, France Inflammation-Immunopathology-Biotherapy Department (DHU i2B), |a184 rue du Faubourg Saint-Antoine, Paris 75012, France.
authors.forename: Meriam
authors.initials: M
authors.lastname: Nefla
authors.affiliation: UMR_S938, CDR Saint-Antoine - INSERM - University Pierre & Marie Curie Paris VI, Sorbonne Universités, 7 quai St-Bernard, Paris 75252, Cedex 5, France Inflammation-Immunopathology-Biotherapy Department (DHU i2B), |a184 rue du Faubourg Saint-Antoine, Paris 75012, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Sudre
authors.affiliation: UMR_S938, CDR Saint-Antoine - INSERM - University Pierre & Marie Curie Paris VI, Sorbonne Universités, 7 quai St-Bernard, Paris 75252, Cedex 5, France Inflammation-Immunopathology-Biotherapy Department (DHU i2B), |a184 rue du Faubourg Saint-Antoine, Paris 75012, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Denat
authors.affiliation: UMR_S938, CDR Saint-Antoine - INSERM - University Pierre & Marie Curie Paris VI, Sorbonne Universités, 7 quai St-Bernard, Paris 75252, Cedex 5, France Inflammation-Immunopathology-Biotherapy Department (DHU i2B), |a184 rue du Faubourg Saint-Antoine, Paris 75012, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Priam
authors.affiliation: INRA, Unité MaIAGE, Mathématiques et Informatique Appliquées du Génome à l'Environnement, UR1404, Jouy-en-Josas F78352, France.
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Andre-Leroux
authors.affiliation: UMR_S938, CDR Saint-Antoine - INSERM - University Pierre & Marie Curie Paris VI, Sorbonne Universités, 7 quai St-Bernard, Paris 75252, Cedex 5, France Inflammation-Immunopathology-Biotherapy Department (DHU i2B), |a184 rue du Faubourg Saint-Antoine, Paris 75012, France Department of Rheumatology, Assistance Publique - Hôpitaux de Paris, Saint-Antoine Hospital, 184 rue du Faubourg Saint-Antoine, Paris 75012, France francis.berenbaum@sat.aphp.fr.
authors.forename: Francis
authors.initials: F
authors.lastname: Berenbaum
authors.affiliation: UMR_S938, CDR Saint-Antoine - INSERM - University Pierre & Marie Curie Paris VI, Sorbonne Universités, 7 quai St-Bernard, Paris 75252, Cedex 5, France Inflammation-Immunopathology-Biotherapy Department (DHU i2B), |a184 rue du Faubourg Saint-Antoine, Paris 75012, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Jacques
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D048948:14-3-3 Proteins; C482983:YWHAE protein, human; C576823:Ywhae protein, mouse; D018826:CD13 Antigens; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse
keywords: 14-3-3ε; Aminopeptidase N; CD13; Chondrocyte; Osteoarthritis