Osteoblast Precursors, but Not Mature Osteoblasts, Move into Developing and Fractured Bones along with Invading Blood Vessels
Open accessAbstract
During endochondral bone development, the first osteoblasts differentiate in the perichondrium surrounding avascular cartilaginous rudiments; the source of trabecular osteoblasts inside the later bone is, however, unknown. Here, we generated tamoxifen-inducible transgenic mice bred to Rosa26R-LacZ reporter mice to follow the fates of stage-selective subsets of osteoblast lineage cells. Pulse-chase studies showed that osterix-expressing osteoblast precursors, labeled in the perichondrium prior to vascular invasion of the cartilage, give rise to trabecular osteoblasts, osteocytes, and stromal cells inside the developing bone. Throughout the translocation, some precursors were found to intimately associate with invading blood vessels, in pericyte-like fashion. A similar coinvasion occurs during endochondral healing of bone fractures. In contrast, perichondrial mature osteoblasts did not exhibit perivascular localization and remained in the outer cortex of developing bones. These findings reveal the specific involvement of immature osteoblast precursors in the coupled vascular and osteogenic transformation essential to endochondral bone development and repair.
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Major regulators within the bone remodeling cascade are BMPs, VEGF, FGF, PDGF, TGF-β1, and IGF-1.
“Among these, major regulators within the bone remodeling cascade are bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-β1 (TGF-β1), and insulin-like growth factor 1 (IGF-1) [39,69,70,71,72,73,74,75,76].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [71]
The Results section on healing fractures (page unavailable) reports VEGF expression and PDGF-Rβ in osteoblast precursors, linking those factors to blood-vessel recruitment during bone repair. It does not identify BMPs, FGF, TGF-β1, or IGF-1 as major regulators, or establish the cited six-factor list for the bone remodeling cascade. (LLM, conf=0.81)
Experimental — accuracy not yet measuredVEGF is essential for angiogenesis and osteogenesis during the normal fracture healing process, facilitating the influx of MSCs that differentiate into osteoblasts via their chemotactic effects.
“VEGF is essential for angiogenesis and osteogenesis during the normal fracture healing process, facilitating the influx of MSCs that differentiate into osteoblasts via their chemotactic effects [39,71,72,83].”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [71]
The Results section (page not specified) reports that osteoblast precursors entered healing fracture tissue alongside invading blood vessels and showed increased VEGF expression. It does not establish that VEGF is essential to fracture healing or that VEGF's chemotactic effects recruit MSCs that then differentiate into osteoblasts. (LLM, conf=0.87)
Experimental — accuracy not yet measuredFollowing bone injury, the bone extracellular matrix releases a physiological amount of growth factors that play a vital role in bone repair.
“Following bone injury, the bone’s extracellular matrix releases a physiological amount of growth factors which play a vital role in bone repair.”
From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [71]
The Results section on healing fractures describes osteoblast precursors moving with blood vessels and reports VEGF and angiopoietin-1 expression in those cells (page unavailable). It does not address growth-factor release from the bone extracellular matrix after injury or the amount released. Searches for matrix-derived growth factors and their release during fracture repair found no passage establishing the claim. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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- Authors
- Maes, C., Kobayashi, T., Selig, M. K., Torrekens, S., Roth, S. I., Mackem, S., Carmeliet, G., & Kronenberg, H. M.
- Affiliations
- Harvard University (US)
- KU Leuven (BE)
- National Cancer Institute (US)
- Corresponding author
- Kronenberg, Henry M.
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 19
- Issue
- 2
- Pages
- 329-344
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC3540406
- OpenAlex
- W2130607897
- Cited by
- 940
- References
- 1
- Citations by year
- 2026: 35 · 2025: 32 · 2024: 63 · 2023: 67 · 2022: 55 · 2021: 55 · 2020: 85 · 2019: 71 · 2018: 62 · 2017: 67 · 2016: 62 · 2015: 69 · 2014: 75 · 2013: 64 · 2012: 37
- FWCI
- 17.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lirias (submittedVersion)
- Funders
- Massachusetts General Hospital
- Fonds Wetenschappelijk Onderzoek
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK056246, P01DK056246)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- osteoblast precursors, endochondral bone development, fracture healing, perichondrium, vascular invasion, pericytes, Osterix, osteocytes, stromal cells, trabecular bone, lineage tracing
- MeSH terms
- Animals, Blood Vessels, Bone and Bones, Bone Development, Bone Regeneration, Cell Movement, Embryo, Mammalian, Female, Male, Mice, Transgenic, Osteoblasts, Pregnancy, Stem Cells, Biomarkers, Cell Lineage, Chondrocytes, Pericytes, Fractures, Bone, Mice
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