Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone
Open accessAbstract
The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms, leading to loss of bone mass and increased fracture incidence. Evidence indicates that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, and pharmacological reversal of this decline allowed the restoration of bone mass.
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Type H vessels support perivascular osteoprogenitor differentiation by producing Noggin via Notch/Dll4 signaling and express CD31 and Endomucin at high levels.
“a specific capillary subtype that supports perivascular osteoprogenitor differentiation by producing Nogging via Notch/Dll 4 signaling has been termed type H vessel, which express both CD31 and Endomucin at high levels.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [128]
Type H vessels are surrounded by abundant osteoprogenitors and are located in the metaphysis and diaphysis.
“Type H vessels are surrounded by abundant osteoprogenitors (Osterix-positive cells) and are located both in the metaphysis, close to the growth plate, and in the diaphysis (periosteum and endosteum).128,129”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [128]
Endothelial specification strongly contributes to bone microarchitectural structures such as cortical versus trabecular bone, and the process of endothelium specification and its mutual interaction with osteogenesis is Notch dependent.
“For bone, it has been demonstrated that endothelial specification strongly contributes to microarchitectural structures—for example, cortical versus trabecular bone. Moreover, there is again an important contribution of Notch signaling since the process of endothelium specification and its mutual interaction with osteogenesis is Notch dependent [146,147,148,149,150].”
From Interactions between Muscle and Bone—Where Physics Meets Biology (2020) · cites this paper as [148]
Endothelial cells are essential for tissue regeneration.
“Endothelial cells (EC) are essential for tissue regeneration.”
From Interactions between Muscle and Bone—Where Physics Meets Biology (2020) · cites this paper as [148]
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- Authors
- Kusumbe, A. P., Ramasamy, S. K., & Adams, R. H.
- Affiliations
- University of Münster (DE)
- Corresponding author
- Adams, Ralf H.
- Venue
- Nature
- Published
- 2014-03-12
- Volume
- 507
- Issue
- 7492
- Pages
- 323-328
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4943525
- OpenAlex
- W2089254126
- Cited by
- 2,155
- References
- 53
- Citations by year
- 2026: 247 · 2025: 231 · 2024: 270 · 2023: 223 · 2022: 222 · 2021: 238 · 2020: 203 · 2019: 136 · 2018: 114 · 2017: 93 · 2016: 76 · 2015: 63 · 2014: 36
- FWCI
- 36.60
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-09-24)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Max-Planck-Gesellschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- angiogenesis, bone formation, bone vascularity, endomucin, CD31, osteoprogenitors, HIF-1α, Notch signaling, bone aging, bone homeostasis, bone regeneration, fracture healing, bone loss
- MeSH terms
- Aging, Animals, Blood Vessels, Bone and Bones, Male, Mice, Inbred C57BL, Osteoblasts, Osteogenesis, Oxygen, Stem Cells, Neovascularization, Physiologic, Endothelial Cells, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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