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Lymphatic vessels in bone support regeneration after injury

Blood and lymphatic vessels form a versatile transport network and provide inductive signals to regulate tissue-specific functions. Blood vessels in bone regulate osteogenesis and hematopoiesis, but current dogma suggests that bone lacks lymphatic vessels. Here, by combining high-resolution light-sh...

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Main Authors: Biswas, Lincoln (Author) , Chen, Junyu (Author) , De Angelis, Jessica (Author) , Singh, Amit (Author) , Owen-Woods, Charlotte (Author) , Ding, Zhangfan (Author) , Pujol, Joan Mane (Author) , Kumar, Naveen (Author) , Zeng, Fanxin (Author) , Ramasamy, Saravana K. (Author) , Kusumbe, Anjali P. (Author)
Format: Article (Journal)
Language:English
Published: January 19, 2023
In: Cell
Year: 2023, Volume: 186, Issue: 2, Pages: 382-397.e24
ISSN:1097-4172
DOI:10.1016/j.cell.2022.12.031
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cell.2022.12.031
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867422015744
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Author Notes:Lincoln Biswas, Junyu Chen, Jessica De Angelis, Amit Singh, Charlotte Owen-Woods, Zhangfan Ding, Joan Mane Pujol, Naveen Kumar, Fanxin Zeng, Saravana K. Ramasamy, and Anjali P. Kusumbe
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Summary:Blood and lymphatic vessels form a versatile transport network and provide inductive signals to regulate tissue-specific functions. Blood vessels in bone regulate osteogenesis and hematopoiesis, but current dogma suggests that bone lacks lymphatic vessels. Here, by combining high-resolution light-sheet imaging and cell-specific mouse genetics, we demonstrate presence of lymphatic vessels in mouse and human bones. We find that lymphatic vessels in bone expand during genotoxic stress. VEGF-C/VEGFR-3 signaling and genotoxic stress-induced IL6 drive lymphangiogenesis in bones. During lymphangiogenesis, secretion of CXCL12 from proliferating lymphatic endothelial cells is critical for hematopoietic and bone regeneration. Moreover, lymphangiocrine CXCL12 triggers expansion of mature Myh11+ CXCR4+ pericytes, which differentiate into bone cells and contribute to bone and hematopoietic regeneration. In aged animals, such expansion of lymphatic vessels and Myh11-positive cells in response to genotoxic stress is impaired. These data suggest lymphangiogenesis as a therapeutic avenue to stimulate hematopoietic and bone regeneration.
Item Description:Gesehen am 14.03.2023
Physical Description:Online Resource
ISSN:1097-4172
DOI:10.1016/j.cell.2022.12.031

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