Mycobacterium tuberculosis specific protein Rv1509 modulates osteoblast and osteoclast differentiation via TLR2 signaling
Summary: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is one of the most ancient diseases recorded. In cases of bone TB, it significantly disrupts bone homeostasis, though the precise mechanisms are poorly understood and effective treatment targets are scarce. Our study investigat...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225003670 |
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| author | Pan Liu Jiezhong Deng Yusheng Yang Wenxi Bai Shengtao Dong Zehua Zhang |
| author_facet | Pan Liu Jiezhong Deng Yusheng Yang Wenxi Bai Shengtao Dong Zehua Zhang |
| author_sort | Pan Liu |
| collection | DOAJ |
| description | Summary: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is one of the most ancient diseases recorded. In cases of bone TB, it significantly disrupts bone homeostasis, though the precise mechanisms are poorly understood and effective treatment targets are scarce. Our study investigated the role of Rv1509 in the pathogenesis of bone TB. We found that Rv1509 enhances the differentiation of bone marrow macrophages (BMMs) into osteoclasts by activating the TLR2 pathway, which stimulates the production of IL-6 and TNF-α. This, in turn, indirectly inhibits osteoblast differentiation and mineralization. Additionally, Rv1509 directly impairs osteoblast function and enhances the secretion of RANKL via TLR2 signaling, creating a detrimental RANKL/OPG imbalance that promotes osteoclast differentiation and bone degradation. Notably, the injection of Rv1509 into mouse skulls led to extensive bone damage, highlighting its significant role as a virulence factor in the pathogenesis of bone TB. |
| format | Article |
| id | doaj-art-fa1a80f4842e4388918f5e4c6af3b255 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-fa1a80f4842e4388918f5e4c6af3b2552025-08-20T02:57:56ZengElsevieriScience2589-00422025-03-0128311210710.1016/j.isci.2025.112107Mycobacterium tuberculosis specific protein Rv1509 modulates osteoblast and osteoclast differentiation via TLR2 signalingPan Liu0Jiezhong Deng1Yusheng Yang2Wenxi Bai3Shengtao Dong4Zehua Zhang5Institute of Department of Orthopedics, Southwest Hospital, Army Medical University, Chongqing 400038, ChinaInstitute of Department of Orthopedics, Southwest Hospital, Army Medical University, Chongqing 400038, ChinaInstitute of Department of Orthopedics, Southwest Hospital, Army Medical University, Chongqing 400038, ChinaInstitute of Department of Orthopedics, Southwest Hospital, Army Medical University, Chongqing 400038, ChinaInstitute of Department of Orthopedics, Southwest Hospital, Army Medical University, Chongqing 400038, ChinaInstitute of Department of Orthopedics, Southwest Hospital, Army Medical University, Chongqing 400038, China; Corresponding authorSummary: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is one of the most ancient diseases recorded. In cases of bone TB, it significantly disrupts bone homeostasis, though the precise mechanisms are poorly understood and effective treatment targets are scarce. Our study investigated the role of Rv1509 in the pathogenesis of bone TB. We found that Rv1509 enhances the differentiation of bone marrow macrophages (BMMs) into osteoclasts by activating the TLR2 pathway, which stimulates the production of IL-6 and TNF-α. This, in turn, indirectly inhibits osteoblast differentiation and mineralization. Additionally, Rv1509 directly impairs osteoblast function and enhances the secretion of RANKL via TLR2 signaling, creating a detrimental RANKL/OPG imbalance that promotes osteoclast differentiation and bone degradation. Notably, the injection of Rv1509 into mouse skulls led to extensive bone damage, highlighting its significant role as a virulence factor in the pathogenesis of bone TB.http://www.sciencedirect.com/science/article/pii/S2589004225003670natural sciencesbiological sciencesbiochemistryphysiologyimmunologymicrobiology |
| spellingShingle | Pan Liu Jiezhong Deng Yusheng Yang Wenxi Bai Shengtao Dong Zehua Zhang Mycobacterium tuberculosis specific protein Rv1509 modulates osteoblast and osteoclast differentiation via TLR2 signaling iScience natural sciences biological sciences biochemistry physiology immunology microbiology |
| title | Mycobacterium tuberculosis specific protein Rv1509 modulates osteoblast and osteoclast differentiation via TLR2 signaling |
| title_full | Mycobacterium tuberculosis specific protein Rv1509 modulates osteoblast and osteoclast differentiation via TLR2 signaling |
| title_fullStr | Mycobacterium tuberculosis specific protein Rv1509 modulates osteoblast and osteoclast differentiation via TLR2 signaling |
| title_full_unstemmed | Mycobacterium tuberculosis specific protein Rv1509 modulates osteoblast and osteoclast differentiation via TLR2 signaling |
| title_short | Mycobacterium tuberculosis specific protein Rv1509 modulates osteoblast and osteoclast differentiation via TLR2 signaling |
| title_sort | mycobacterium tuberculosis specific protein rv1509 modulates osteoblast and osteoclast differentiation via tlr2 signaling |
| topic | natural sciences biological sciences biochemistry physiology immunology microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225003670 |
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