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Specialized post-arterial capillaries facilitate adult bone remodelling
Nature Cell Biology ( IF 17.3 ) Pub Date : 2024-11-11 , DOI: 10.1038/s41556-024-01545-1
Vishal Mohanakrishnan, Kishor K. Sivaraj, Hyun-Woo Jeong, Esther Bovay, Backialakshmi Dharmalingam, M. Gabriele Bixel, Van Vuong Dinh, Milena Petkova, Isidora Paredes Ugarte, Yi-Tong Kuo, Malarvizhi Gurusamy, Brian Raftrey, Nelson Tsz Long Chu, Soumyashree Das, Pamela E. Rios Coronado, Martin Stehling, Lars Sävendahl, Andrei S. Chagin, Taija Mäkinen, Kristy Red-Horse, Ralf H. Adams

The vasculature of the skeletal system is crucial for bone formation, homoeostasis and fracture repair, yet the diversity and specialization of bone-associated vessels remain poorly understood. Here we identify a specialized type of post-arterial capillary, termed type R, involved in bone remodelling. Type R capillaries emerge during adolescence around trabecular bone, possess a distinct morphology and molecular profile, and are associated with osteoprogenitors and bone-resorbing osteoclasts. Endothelial cell-specific overexpression of the transcription factor DACH1 in postnatal mice induces a strong increase in arteries and type R capillaries, leading to local metabolic changes and enabling trabecular bone formation in normally highly hypoxic areas of the diaphysis. Indicating potential clinical relevance of type R capillaries, these vessels respond to anti-osteoporosis treatments and emerge during ageing inside porous structures that are known to weaken compact bone. Our work outlines fundamental principles of vessel specialization in the developing, adult and ageing skeletal system.



中文翻译:


专门的动脉后毛细血管促进成人骨重塑



骨骼系统的脉管系统对于骨形成、匀态和骨折修复至关重要,但人们对骨相关血管的多样性和专业化仍然知之甚少。在这里,我们确定了一种特殊类型的动脉后毛细血管,称为 R 型,参与骨重塑。R 型毛细血管在青春期出现在骨小梁周围,具有独特的形态和分子特征,并与骨祖细胞和骨吸收破骨细胞有关。出生后小鼠转录因子 DACH1 的内皮细胞特异性过表达诱导动脉和 R 型毛细血管的强烈增加,导致局部代谢变化,并在骨干的正常高度缺氧区域形成小梁骨。这些血管表明 R 型毛细血管的潜在临床相关性,这些血管对抗骨质疏松症治疗有反应,并在衰老过程中出现在已知会削弱致密骨骼的多孔结构内。我们的工作概述了发育中、成人和衰老骨骼系统中血管专业化的基本原则。

更新日期:2024-11-12
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