title: Brucella abortus invasion of synoviocytes inhibits apoptosis and induces bone resorption through RANKL expression.
abstract: Arthritis is one of the most common complications of human active brucellosis, but its pathogenic mechanisms have not been completely elucidated. In this paper, we describe the role of synoviocytes in the pathogenesis of brucellar arthritis. Our results indicate that Brucella abortus infection inhibited synoviocyte apoptosis through the upregulation of antiapoptotic factors (cIAP-2, clusterin, livin, and P21/CIP/CDNK1A). In contrast, infection did not change the expression of proteins that have been involved in apoptosis induction such as Bad, Bax, cleaved procaspase 3, CytC, and TRAIL, among others; or their expression was reduced, as occurs in the case of P-p53(S15). In addition, B. abortus infection induced upregulation of adhesion molecules (CD54 and CD106), and the adhesion of monocytes and neutrophils to infected synoviocytes was significantly higher than to uninfected cells. Despite this increased adhesion, B. abortus-infected synoviocytes were able to inhibit apoptosis induced by supernatants from B. abortus-infected monocytes and neutrophils. Moreover, B. abortus infection increased soluble and membrane RANKL expression in synoviocytes that further induced monocytes to undergo osteoclastogenesis. The results presented here shed light on how the interactions of B. abortus with synovial fibroblasts may have an important role in the pathogenesis of brucellar arthritis.
authors.affiliation: Instituto de Inmunología, Genética y Metabolismo (INIGEM), Hospital de Clínicas "José de San Martín," Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Romina
authors.initials: R
authors.lastname: Scian
authors.forename: Paula
authors.initials: P
authors.lastname: Barrionuevo
authors.forename: Ana María
authors.initials: AM
authors.lastname: Rodriguez
authors.forename: Paula Constanza
authors.initials: PC
authors.lastname: Arriola Benitez
authors.forename: Clara
authors.initials: C
authors.lastname: García Samartino
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Fossati
authors.forename: Guillermo Hernán
authors.initials: GH
authors.lastname: Giambartolomei
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Delpino
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D001862:Bone Resorption / Q000378:metabolism; D002003:Brucella abortus / Q000502:physiology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006801:Humans; D010010:Osteoclasts / Q000378:metabolism / Q000382:microbiology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D053245:RANK Ligand; C505688:TNFSF11 protein, human