ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Bacterial Pathogenesis
This article is part of the Research TopicZoonotic Bacterial Pathogens: Infection and Host InteractionView all 8 articles
Brucella melitensis Clinical Isolate Modulates Osteoclast Differentiation to Drive Pathological Bone Destruction in Brucellar Arthritis
Provisionally accepted
- 1Lanzhou University Second Hospital, Lanzhou, China
- 2Lanzhou University, Lanzhou, China
- 3Lanzhou Veterinary Research Institute Chinese Academy of Agricultural Sciences, Lanzhou, China
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Background: 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 Brucella-induced bone destruction, but the direct cellular tropism of Brucella within bone tissue and the specific effects of infection on osteoclasts remain poorly understood. This study aims to characterize the osteoclast tropism of Brucella melitensis biovar 3 clinical isolates and their direct regulatory effects on osteoclast-mediated bone destruction in Brucella-induced arthritis. Methods: Brucella 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. Results: Three clinical isolates of B. melitensis biovar 3 were obtained from arthritis lesions in patients from Gansu. Genomic analysis revealed homology with geographically diverse Chinese Brucella 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.
Keywords: B. melitensis biovar 3, Bone Resorption, Brucellar arthritis, Osteoclast differentiation and function, pathological bone destruction
Received: 28 Aug 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Chen, Feijie, Zhao, Su, Tuo, Song, Chu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Haihong Zhang
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