{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:01:19Z","timestamp":1793836879527,"version":"4.6.1"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella abortus<\/jats:named-content>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<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>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<jats:italic>B. abortus-<\/jats:italic>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-\u03b1). These results indicate that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. abortus<\/jats:named-content>may directly and indirectly harm osteoblast function, contributing to the bone and joint destruction observed in patients with osteoarticular complications of brucellosis.<\/jats:p>","DOI":"10.1128\/iai.00208-12","type":"journal-article","created":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T03:14:59Z","timestamp":1335842099000},"page":"2333-2345","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Brucella abortus Invasion of Osteoblasts Inhibits Bone Formation"],"prefix":"10.1128","volume":"80","author":[{"given":"Romina","family":"Scian","sequence":"first","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Laboratorio de Inmunogen\u00e9tica, Hospital de Cl\u00ednicas Jos\u00e9 de San Mart\u00edn, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Barrionuevo","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Laboratorio de Inmunogen\u00e9tica, Hospital de Cl\u00ednicas Jos\u00e9 de San Mart\u00edn, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Fossati","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo H.","family":"Giambartolomei","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Laboratorio de Inmunogen\u00e9tica, Hospital de Cl\u00ednicas Jos\u00e9 de San Mart\u00edn, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Victoria","family":"Delpino","sequence":"additional","affiliation":[{"name":"Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioqu\u00edmica, Universidad de Buenos Aires, Buenos Aires, Argentina"},{"name":"Laboratorio de Inmunogen\u00e9tica, Hospital de Cl\u00ednicas Jos\u00e9 de San Mart\u00edn, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.mnm.0000167651.52724.68"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.7.4858"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.6.2804-2809.1999"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-6009(91)90100-E"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2302\/kjm.54.127"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_3_2_8_2","first-page":"27","article-title":"Bone structure and function","volume":"36","author":"Buckwalter JA","year":"1987","unstructured":"BuckwalterJACooperRR. 1987. Bone structure and function. Instr. Course Lect. 36:27\u201348.","journal-title":"Instr. Course Lect."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.4049\/jimmunol.156.8.2885","article-title":"Brucella species release a specific, protease-sensitive, inhibitor of TNF-alpha expression, active on human macrophage-like cells","volume":"156","author":"Caron E","year":"1996","unstructured":"CaronEGrossALiautardJPDornandJ. 1996. Brucella species release a specific, protease-sensitive, inhibitor of TNF-alpha expression, active on human macrophage-like cells. J. Immunol. 156:2885\u20132893.","journal-title":"J. Immunol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071924"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018748"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/525266"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.04111185"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.02.028"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01259-08"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090503"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.09.005"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)89580-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/ortho\/25.2.101"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"5550","DOI":"10.4049\/jimmunol.159.11.5550","article-title":"Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal epithelial cells","volume":"159","author":"Hobbie S","year":"1997","unstructured":"HobbieSChenLMDavisRJGalanJE. 1997. Involvement of mitogen-activated protein kinase pathways in the nuclear responses and cytokine production induced by Salmonella typhimurium in cultured intestinal epithelial cells. J. Immunol. 159:5550\u20135559.","journal-title":"J. Immunol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/mp.50.3.132"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-6757(97)90173-X"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2460\/javma.1992.201.08.1253","article-title":"Diskospondylitis associated with Brucella canis infection in dogs: 14 cases (1980\u20131991)","volume":"201","author":"Kerwin SC","year":"1992","unstructured":"KerwinSC. 1992. Diskospondylitis associated with Brucella canis infection in dogs: 14 cases (1980\u20131991). J. Am. Vet. Med. Assoc. 201:1253\u20131257.","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1081\/IPH-120014725"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/46303"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.08.025"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1039060"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.12.6244"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(95)00076-P"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.37"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00311.2006"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.12.048"},{"key":"e_1_3_2_33_2","first-page":"2096","article-title":"Brucellosis-induced murine arthritis and spondylolisthesis","volume":"63","author":"Lyons E","year":"2011","unstructured":"LyonsEMagnaniDForde ToniSSplitterGAdarichev VyacheslavA. 2011. Brucellosis-induced murine arthritis and spondylolisthesis. Arthritis Rheum. 63(Suppl 10):2096.","journal-title":"Arthritis Rheum."},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/978-3-642-59533-2_10","volume-title":"Madkour's brucellosis","author":"Madkour MM","year":"2001","unstructured":"MadkourMM. 2001. Bone and joint imaging, p 90\u2013132. In MadkourMM (ed), Madkour's brucellosis, 2nd ed. Springer-Verlag, Berlin, Germany.","edition":"2"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/978-3-642-59533-2_8","volume-title":"Madkour's brucellosis","author":"Madkour MM","year":"2001","unstructured":"MadkourMM. 2001. Osteoarticular brucellosis, p 74\u201387. In MadkourMM (ed), Madkour's brucellosis, 2nd ed. Springer-Verlag, Berlin, Germany.","edition":"2"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.09.063"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1757-7861.2011.00146.x"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01534267"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2009.0345"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0950-3579(05)80153-0"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10097"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026720003564"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00934-10"},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","first-page":"986","DOI":"10.2460\/javma.1987.191.08.986","article-title":"Brucella canis osteomyelitis in two dogs with total hip replacements","volume":"191","author":"Smeak DD","year":"1987","unstructured":"SmeakDDOlmsteadMLHohnRB. 1987. Brucella canis osteomyelitis in two dogs with total hip replacements. J. Am. Vet. Med. Assoc. 191:986\u2013990.","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.3109\/00313029209063615"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00228-08"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-1050-9_7"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.6.2359-2361.1996"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.3.1106-1112.1998"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2011.08.015"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2005.10.013"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.32207"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004180050447"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar431"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.8.3167"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2009.05.008"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1159\/000053631"},{"key":"e_1_3_2_58_2","volume-title":"Brucellosis: clinical and laboratory aspects","author":"Young EJ","year":"1989","unstructured":"YoungEJ. 1989. Clinical manifestations of human brucellosis. In YoungEJCorbelMJ, (ed) Brucellosis: clinical and laboratory aspects. CRC Press, Boca Raton, FL."}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00208-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00208-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T23:34:47Z","timestamp":1743032087000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00208-12"}},"subtitle":[],"editor":[{"given":"A.","family":"Camilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,7]]},"references-count":57,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,7]]}},"alternative-id":["10.1128\/IAI.00208-12"],"URL":"https:\/\/doi.org\/10.1128\/iai.00208-12","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7]]},"assertion":[{"value":"2012-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-04-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-06-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}