TY - JOUR
T1 - Specialized post-arterial capillaries facilitate adult bone remodelling
AU - Mohanakrishnan, Vishal
AU - Sivaraj, Kishor K.
AU - Jeong, Hyun Woo
AU - Bovay, Esther
AU - Dharmalingam, Backialakshmi
AU - Bixel, M. Gabriele
AU - Dinh, Van Vuong
AU - Petkova, Milena
AU - Paredes Ugarte, Isidora
AU - Kuo, Yi Tong
AU - Gurusamy, Malarvizhi
AU - Raftrey, Brian
AU - Chu, Nelson Tsz Long
AU - Das, Soumyashree
AU - Rios Coronado, Pamela E.
AU - Stehling, Martin
AU - Sävendahl, Lars
AU - Chagin, Andrei S.
AU - Mäkinen, Taija
AU - Red-Horse, Kristy
AU - Adams, Ralf H.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
KW - 1182 Biochemistry, cell and molecular biology
U2 - 10.1038/s41556-024-01545-1
DO - 10.1038/s41556-024-01545-1
M3 - Article
AN - SCOPUS:85208941142
SN - 1465-7392
VL - 26
SP - 2020
EP - 2034
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 12
ER -