Establishment of a biosafe murine model of skeletal tuberculosis using Mycobacterium smegmatisOA
Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.
Yewei Jia;Yuhuai Guo;Yusheng Yang;Jie Zhang;Ziyang Zhang;Ying Qu;Jiulin Tan;Jie Shen;Nathachit Limjunyawong;Jianzhong Xu;Zehua Zhang;Fei Luo;Ce Dou
Department of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,China Center of Research Excellence in Allergy&Immunology,Research Department,Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,ThailandDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaCenter of Research Excellence in Allergy&Immunology,Research Department,Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,ThailandDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,ChinaDepartment of Orthopaedics,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing,China
医药卫生
bone tuberculosismurine modelMycobacterium smegmatistuberculosis
《Animal Models and Experimental Medicine》 2026 (1)
P.5-20,16
Southwest Hospital Boqing Innovation Fund,Grant/Award Number:2024BQCXJJ-9Fundings for Young Investigators of PLA,Grant/Award Number:2022-JCJQ-QT-004NSFC Key Projects of the Regional Innovation and Development Joint Fund,Grant/Award Number:U23A20413China Postdoctoral Science Foundation,Grant/Award Number:2023M744280National Natural Science Foundation of China,Grant/Award Number:82103778,82172449 and 82172489Southwest Hospital Postdoctoral Starting Fund,Grant/Award Number:5175ZA36BP。
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