{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T10:05:23Z","timestamp":1780394723907,"version":"3.54.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Brucellosis is a widespread zoonosis that is acquired by humans from infected animals. Articular complications, particularly brucellar spondylitis, are the most prevalent and disabling manifestations of human brucellosis. Inflammation-mediated osteoclast activation is implicated in\n                      <jats:italic>Brucella<\/jats:italic>\n                      -induced bone destruction, but the direct cellular tropism of\n                      <jats:italic>Brucella<\/jats:italic>\n                      within bone tissue and the specific effects of infection on osteoclasts remain poorly understood. This study aims to characterize the osteoclast tropism of\n                      <jats:italic>Brucella melitensis<\/jats:italic>\n                      biovar 3 clinical isolates and their direct regulatory effects on osteoclast-mediated bone destruction in\n                      <jats:italic>Brucella<\/jats:italic>\n                      -induced arthritis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Brucella<\/jats:italic>\n                      clinical isolates were obtained from the bone tissues of human brucellar spondylitis patients in Gansu Province, China. Whole-genome sequencing and biotyping identified their specific biovars. These isolates were used to generate arthritis in immunodeficient NCG mice; bone homeostasis in these mice was assessed via ELISA. We assessed their cellular tropism and osteoclast-modulating effects through intracellular survival assays, immunofluorescence, histopathology, TRAP staining, and resorption pit analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three clinical isolates of\n                      <jats:italic>B. melitensis<\/jats:italic>\n                      biovar 3 were obtained from arthritis lesions in patients from Gansu. Genomic analysis revealed homology with geographically diverse Chinese\n                      <jats:italic>Brucella<\/jats:italic>\n                      strains. Although these isolates reached splenic bacterial loads similar to the virulent strain 16M, they did not cause splenomegaly by two weeks post-infection. The isolates displayed strong tropism for human and murine osteoclasts, achieving significantly higher intracellular loads compared to osteoblasts or osteocytes. Infection at the osteoclast precursor\/bone marrow macrophage stage enhanced early osteoclastogenesis while inhibiting late-stage apoptosis and fusion, leading to prolonged osteoclast survival and aggravated bone resorption and defects. In contrast, conditioned medium from infected osteoblasts or osteocytes had minimal impact on late-stage osteoclast differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings elucidate the mechanisms underlying pathological bone defects in brucellar arthritis. The direct bacterial effects, together with the formation of an osteoclast-derived pro-survival niche, account for the prevalence of brucellar arthritis as the most common complication of chronic brucellosis. Targeting the interaction between\n                      <jats:italic>B. melitensis<\/jats:italic>\n                      and osteoclasts may thus offer a novel therapeutic strategy for preventing and treating\n                      <jats:italic>Brucella<\/jats:italic>\n                      -induced osteolytic lesions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1694633","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T06:33:49Z","timestamp":1765521229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Brucella melitensis clinical isolate modulates osteoclast differentiation to drive pathological bone destruction in brucellar arthritis"],"prefix":"10.3389","volume":"15","author":[{"given":"Jinlei","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feijie","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghai","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyun","family":"Tuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefeng","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1186\/s12879-021-06538-1","article-title":"Isolation of Brucella abortus biovar 1 from human lumbar disc bulging: a case report of brucellar discitis","volume":"21","author":"Alamian","year":"2021","journal-title":"BMC Infect. 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