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
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引用次数: 0
摘要
骨骼系统的血管对骨的形成、平衡和骨折修复至关重要,但人们对骨相关血管的多样性和特化仍知之甚少。在这里,我们发现了一种参与骨重塑的特化后动脉毛细血管类型,称为 R 型。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,并与成骨细胞和骨吸收破骨细胞相关。在出生后的小鼠体内,内皮细胞特异性过量表达转录因子 DACH1 会诱导动脉和 R 型毛细血管的大量增加,从而导致局部新陈代谢发生变化,并使干骺端通常高度缺氧的区域形成骨小梁。这些血管对抗骨质疏松症治疗有反应,并在已知会削弱骨密度的多孔结构内老化过程中出现,这表明 R 型毛细血管具有潜在的临床意义。我们的工作概述了发育中、成年和老化骨骼系统中血管特化的基本原理。
Specialized post-arterial capillaries facilitate adult bone remodelling
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. Mohanakrishnan et al. identify a distinct subset of post-arterial capillaries, termed type R. They show that type R capillaries contribute to trabecular bone formation in the diaphysis and respond to anti-osteoporosis treatments.
期刊介绍:
Nature Cell Biology, a prestigious journal, upholds a commitment to publishing papers of the highest quality across all areas of cell biology, with a particular focus on elucidating mechanisms underlying fundamental cell biological processes. The journal's broad scope encompasses various areas of interest, including but not limited to:
-Autophagy
-Cancer biology
-Cell adhesion and migration
-Cell cycle and growth
-Cell death
-Chromatin and epigenetics
-Cytoskeletal dynamics
-Developmental biology
-DNA replication and repair
-Mechanisms of human disease
-Mechanobiology
-Membrane traffic and dynamics
-Metabolism
-Nuclear organization and dynamics
-Organelle biology
-Proteolysis and quality control
-RNA biology
-Signal transduction
-Stem cell biology