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.
Authors
- Van Vuong Dinh
- Brian Raftrey
- Hyun‐Woo Jeong (ORCID: https://orcid.org/0000-0002-6976-6739)
- Pamela E. Rios Coronado (ORCID: https://orcid.org/0000-0003-4665-6438)
- Martin Stehling (ORCID: https://orcid.org/0000-0002-0827-6357)
- Andrei S. Chagin (ORCID: https://orcid.org/0000-0002-2696-5850)
- Soumyashree Das (ORCID: https://orcid.org/0000-0003-1236-3194)
- Lars Sävendahl (ORCID: https://orcid.org/0000-0003-1067-4976)
- Yien–Ming Kuo
- Milena Petkova (ORCID: https://orcid.org/0000-0002-7186-7256)
- Esther Bovay (ORCID: https://orcid.org/0000-0002-9984-1269)
- Ralf H. Adams (ORCID: https://orcid.org/0000-0003-3031-7677)
- Vishal Mohanakrishnan (ORCID: https://orcid.org/0000-0003-0976-9230)
- M. Gabriele Bixel (ORCID: https://orcid.org/0000-0001-8656-8075)
- Taija Mäkinen (ORCID: https://orcid.org/0000-0002-9338-1257)
- Malarvizhi Gurusamy
- Kristy Red‐Horse (ORCID: https://orcid.org/0000-0003-1541-601X)
- Kishor K. Sivaraj (ORCID: https://orcid.org/0000-0002-5321-3400)
- Nelson Tsz Long Chu
- Backialakshmi Dharmalingam (ORCID: https://orcid.org/0000-0003-2922-0501)
- Isidora Paredes Ugarte
Institutions
- Tata Institute of Fundamental Research (IN)
- Uppsala University (SE)
- Karolinska University Hospital (SE)
- University of Helsinki (FI)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- National Centre for Biological Sciences (IN)
- California Institute for Regenerative Medicine (US)
- Cardiovascular Institute of the South (US)
- Karolinska Institutet (SE)
- Wihuri Research Institute (FI)
- Max Planck Institute for Molecular Biomedicine (DE)
- University of Gothenburg (SE)
- Stanford University (US)
Publication Details
- Journal
- Nature Cell Biology
- Published
- 2024-11-11
- DOI
- https://doi.org/10.1038/s41556-024-01545-1
- Citations
- 28
- Primary Topic
- Bone Metabolism and Diseases
- Type
- article
- Field-Weighted Citation Impact
- 6.55