title: Brucella abortus invasion of osteoblasts inhibits bone formation.
abstract: Osteoarticular brucellosis is the most common presentation of the active disease in humans. Loss of bone is a serious complication of localized bacterial infection of bones or the adjacent tissue, and brucellosis proved not to be the exception. The skeleton is a dynamic organ system which is constantly remodeled. Osteoblasts are responsible for the deposition of bone matrix and are thought to facilitate the calcification and mineralization of the bone matrix, and their function could be altered under infectious conditions. In this article, we describe immune mechanisms whereby Brucella abortus may invade and replicate within osteoblasts, inducing apoptosis, inhibiting mineral and organic matrix deposition, and inducing upregulation of RANKL expression. Additionally, all of these mechanisms contributed in different ways to bone loss. These processes implicate the activation of signaling pathways (mitogen-activated protein kinases [MAPK] and caspases) involved in cytokine secretion, expression of activating molecules, and cell death of osteoblasts. In addition, considering the relevance of macrophages in intracellular Brucella survival and proinflammatory cytokine secretion in response to infection, we also investigated the role of these cells as modulators of osteoblast survival, differentiation, and function. We demonstrated that supernatants from B. abortus-infected macrophages may also mediate osteoblast apoptosis and inhibit osteoblast function in a process that is dependent on the presence of tumor necrosis factor alpha (TNF-α). These results indicate that B. abortus may directly and indirectly harm osteoblast function, contributing to the bone and joint destruction observed in patients with osteoarticular complications of brucellosis.
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral-IDEHU, Facultad de Farmacia y Bioquímica, 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: Carlos A
authors.initials: CA
authors.lastname: Fossati
authors.forename: Guillermo H
authors.initials: GH
authors.lastname: Giambartolomei
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Delpino
mesh_terms: D000818:Animals; D017209:Apoptosis; D002003:Brucella abortus / Q000472:pathogenicity*; D002478:Cells, Cultured; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000382:microbiology*; D010012:Osteogenesis