Brucella abortus Invasion of Synoviocytes Inhibits Apoptosis and Induces Bone Resorption through RANKL Expression

SCIAN R; BARRIONUEVO P,; RODRIGUEZ ANA MARIA; ARRIOLA BENITEZ PC; SAMARTINO C, GARCIA; FOSSATI, CA; GIAMBARTOLOMEI GH,; DELPINO MV

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2013 vol. 81 p. 1940 - 1951

0019-9567

Arthritis is one of the most common complications of human active brucellosis, but its pathogenic mechanisms have not been completelyelucidated. In this paper, we describe the role of synoviocytes in the pathogenesis of brucellar arthritis. Our results indicate thatBrucella 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 inductionsuch as Bad, Bax, cleaved procaspase 3, CytC, and TRAIL, among others; or their expression was reduced, as occurs in the case ofP-p53(S15). In addition, B. abortus infection induced upregulation of adhesion molecules (CD54 and CD106), and the adhesion ofmonocytes 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 inducedmonocytes to undergo osteoclastogenesis. The results presented here shed light on how the interactions of B. abortus with synovialfibroblasts may have an important role in the pathogenesis of brucellar arthritis.