Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs
Abstract In the musculoskeletal system, lymphatic vessels (LVs), which are interdigitated with blood vessels, travel and form an extensive transport network. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, we inves...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56147-8 |
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| author | Yangkang Zheng Lin Cong Li Zhao Pengyu Wang Lianping Xing Junling Liu Hao Xu Ning Li Yongjian Zhao Luying Yuan Qi Shi Xueqing Sun Qianqian Liang YongJun Wang |
| author_facet | Yangkang Zheng Lin Cong Li Zhao Pengyu Wang Lianping Xing Junling Liu Hao Xu Ning Li Yongjian Zhao Luying Yuan Qi Shi Xueqing Sun Qianqian Liang YongJun Wang |
| author_sort | Yangkang Zheng |
| collection | DOAJ |
| description | Abstract In the musculoskeletal system, lymphatic vessels (LVs), which are interdigitated with blood vessels, travel and form an extensive transport network. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, we investigate the lymphatic draining function at the tibial fracture sites using near-infrared indocyanine green lymphatic imaging (NIR-ICG) and discover that lymphatic drainage insufficiency (LDI) starts on day one and persists for up to two weeks following the fracture in male mice. Sufficient lymphatic drainage facilitates fracture healing in male mice. Furthermore, we identify that lymphatic platelet thrombosis (LPT) blocks the draining lymphoid sinus and LVs, causes LDI, and inhibits fracture healing in male mice, which can be rescued by a blood thinner. Moreover, unblocked lymphatic drainage decreases neutrophils and increases M2-type macrophages of the hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs) in male rats. Lymphatic platelet thrombolysis also benefits senile fracture healing in female mice. These findings demonstrate that LPT limits bone regeneration by impeding lymphatic transporting DAMPs. Together, these findings represent a way forward in the treatment of bone repair. |
| format | Article |
| id | doaj-art-7617a0b72c27468586e763b8ba886502 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-7617a0b72c27468586e763b8ba8865022025-01-19T12:31:14ZengNature PortfolioNature Communications2041-17232025-01-0116112510.1038/s41467-025-56147-8Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPsYangkang Zheng0Lin Cong1Li Zhao2Pengyu Wang3Lianping Xing4Junling Liu5Hao Xu6Ning Li7Yongjian Zhao8Luying Yuan9Qi Shi10Xueqing Sun11Qianqian Liang12YongJun Wang13Longhua Hospital, Shanghai University of Traditional Chinese MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Pathology and Laboratory Medicine and Center for Musculoskeletal Research, University of Rochester Medical CenterDepartment of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineLonghua Hospital, Shanghai University of Traditional Chinese MedicineAbstract In the musculoskeletal system, lymphatic vessels (LVs), which are interdigitated with blood vessels, travel and form an extensive transport network. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, we investigate the lymphatic draining function at the tibial fracture sites using near-infrared indocyanine green lymphatic imaging (NIR-ICG) and discover that lymphatic drainage insufficiency (LDI) starts on day one and persists for up to two weeks following the fracture in male mice. Sufficient lymphatic drainage facilitates fracture healing in male mice. Furthermore, we identify that lymphatic platelet thrombosis (LPT) blocks the draining lymphoid sinus and LVs, causes LDI, and inhibits fracture healing in male mice, which can be rescued by a blood thinner. Moreover, unblocked lymphatic drainage decreases neutrophils and increases M2-type macrophages of the hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs) in male rats. Lymphatic platelet thrombolysis also benefits senile fracture healing in female mice. These findings demonstrate that LPT limits bone regeneration by impeding lymphatic transporting DAMPs. Together, these findings represent a way forward in the treatment of bone repair.https://doi.org/10.1038/s41467-025-56147-8 |
| spellingShingle | Yangkang Zheng Lin Cong Li Zhao Pengyu Wang Lianping Xing Junling Liu Hao Xu Ning Li Yongjian Zhao Luying Yuan Qi Shi Xueqing Sun Qianqian Liang YongJun Wang Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs Nature Communications |
| title | Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs |
| title_full | Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs |
| title_fullStr | Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs |
| title_full_unstemmed | Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs |
| title_short | Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs |
| title_sort | lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting damps |
| url | https://doi.org/10.1038/s41467-025-56147-8 |
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