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Publication : Lymphatic vessels in bone support regeneration after injury.

First Author  Biswas L Year  2023
Journal  Cell Volume  186
Issue  2 Pages  382-397.e24
PubMed ID  36669473 Mgi Jnum  J:336258
Mgi Id  MGI:7432232 Doi  10.1016/j.cell.2022.12.031
Citation  Biswas L, et al. (2023) Lymphatic vessels in bone support regeneration after injury. Cell 186(2):382-397.e24
abstractText  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.
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