ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2019
Regulation of the Bone Vascular Network is Sexually Dimorphic.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- TNAP and PHOSPHO1 Function Synergistically to Afford Critical Control Over the Mineralization of the Postnatal Murine Skeleton.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TNAP and PHOSPHO1 function synergistically to afford critical control over the mineralisation of the postnatal murine skeleton.bioRxiv : the preprint server for biology · 2026Article
- Cortical bone porosity is spatially heterogeneous and VEGF dependent in male bone.Disease models & mechanisms · 2026Article
- Synergistic promotion of bone regeneration through co-culture of endothelial cells with mesenchymal stem cells in endochondral ossification organoids.Stem cell research & therapy · 2025Article
- COX-2 in Fracture Callus Chondro-Osseous Junction Osteoclasts Regulates Chondrocyte Hypertrophy and Callus Vasculogenesis.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
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- Sexually dimorphic effects of prenatal alcohol exposure on the murine skeleton.Biology of sex differences · 2024Article
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- Persistent homology analysis distinguishes pathological bone microstructure in non-linear microscopy images.Scientific reports · 2023Article
- Long-Term Cola Intake Does Not Cause Evident Pathological Alterations in the Femoral Bone Microstructure: An Animal Study in Adult Mice.Nutrients · 2023Article
- Sexing Bones: Improving Transparency of Sex Reporting to Address Bias Within Preclinical Studies.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Skeletal effects following developmental flame-retardant exposure are specific to sex and chemical class in the adult Wistar rat.Frontiers in toxicology · 2023Article
- Sex-Based Difference in Bone Healing: A Review of Recent Pre-clinical Literature.Current reviews in musculoskeletal medicine · 2022Review
- Article
- Sex differences and altered mitophagy in experimental pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Suture Cells in a Mechanical Stretching Niche: Critical Contributors to Trans-sutural Distraction Osteogenesis.Calcified tissue international · 2022Review
- Temporal and Quantitative Transcriptomic Differences Define Sexual Dimorphism in Murine Postnatal Bone Aging.JBMR plus · 2022Article
- Multiscale molecular profiling of pathological bone resolves sexually dimorphic control of extracellular matrix composition.Disease models & mechanisms · 2021Article
- A robust, semi-automated approach for counting cementum increments imaged with synchrotron X-ray computed tomography.PloS one · 2021Article
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Osteoblast (OB) lineage cells are an important source of vascular endothelial growth factor (VEGF), which is critical for bone growth and repair. During bone development, pubertal differences in males and females exist, but little is known about whether VEGF signaling contributes to skeletal sexual dimorphism. We have found that in mice, conditional disruption of VEGF in osteocalcin-expressing cells (OcnVEGFKO) exerts a divergent influence on morphological, cellular, and whole bone properties between sexes. Furthermore, we describe an underlying sexual divergence in VEGF signaling in OB cultures in vitro independent of circulating sex hormones. High-resolution synchrotron computed tomography and backscattered scanning electron microscopy revealed, in males, extensive unmineralized osteoid encasing enlarged blood vessel canals and osteocyte lacunae in cortical bone after VEGF deletion, which contributed to increased porosity. VEGF was deleted in male and female long bone-derived OBs (OBVEGKO) in vitro and Raman spectroscopic analyses of mineral and matrix repertoires highlighted differences between male and female OBVEGFKO cells, with increased immature phosphate species prevalent in male OBVEGFKO cultures versus wild type (WT). Further sexual dimorphism was observed in bone marrow endothelial cell gene expression in vitro after VEGF deletion and in sclerostin protein expression, which was increased in male OcnVEGFKO bones versus WT. The impact of altered OB matrix composition after VEGF deletion on whole bone geometry was assessed between sexes, although significant differences between OcnVEGFKO and WT were identified only in females. Our results suggest that bone-derived VEGF regulates matrix mineralization and vascularization distinctly in males and females, which results in divergent physical bone traits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.