ArticleThe Journal of clinical investigation2023
Bone-derived PDGF-BB drives brain vascular calcification in male mice.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Osteogenic-like Phenotypic Reprogramming Is Associated with Reduced Malignant Behaviors in Pancreatic Cancer Cells Involving MAPK-ERK Signaling.International journal of molecular sciences · 2026Article
- Analysis of the effect of platelet-derived growth factor combined with T cells in the diagnosis of hepatocellular carcinoma and prognostic assessment: A prospective cohort study.Journal of medical biochemistry · 2026Article
- A FZD4/LRP5 agonist restores pericyte coverage and vascular integrity by increasing PDGFB signaling.bioRxiv : the preprint server for biology · 2026Article
- Considerations in the Use of Mouse Models of Vascular and Valvular Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- The therapeutic potential of descending regulatory pathways from brain to bone in osteoporosis: focusing on the brain-bone axis.Frontiers in endocrinology · 2026Review
- Beyond resorption: targeting osteoclast fusion and polarization to restore balanced bone remodeling.Frontiers in pharmacology · 2026Review
- Platelet-derived growth factor-BB (PDGF-BB): pathophysiological roles and therapeutic implications in aging-related diseases.Frontiers in cell and developmental biology · 2026Review
- PDGF signaling in cartilage regeneration: molecular mechanisms and cellular effects.Frontiers in cell and developmental biology · 2026Review
- Injured bone-triggered osteokines secretion promotes diabetic wound healing.Bone research · 2025Article
- Article
- Umbilical Cord-Mesenchymal Stromal Cell-Derived Extracellular Vesicles Target the Liver to Improve Neurovascular Health in Type 2 Diabetes With Non-Alcoholic Fatty Liver Disease.Journal of extracellular vesicles · 2025Article
- Elevated phosphate levels in CKD - a direct threat for the heart.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Histogram-based analysis for confocal microscope images with immunofluorescent staining: A graphical-user-interface tool.MethodsX · 2025Article
- Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs.Bone research · 2025Review
- Use of Mesenchymal Stem Cell-Targeting 3WJ Nanoparticles and Reported Specific Delivery of Anti-miRNA 138 to Treat Osteoporosis.ACS omega · 2025Article
- Vascular Ossification in the Developing Brain: A Case Study of Pediatric Sturge Weber Syndrome.Neuroscience bulletin · 2025Article
- CPP-calcification of articular cartilage is associated with elevated cytokine levels in synovial fluid.Frontiers in cell and developmental biology · 2025Article
- Bone marrow mesenchymal stem cell-derived exosomal microRNA-335 alleviates vascular calcification by targeting SP1.Frontiers in cardiovascular medicine · 2025Article
- Platelet-derived growth factor subunit B overexpression promotes lung cancer tumor growth and metastasis: The role of glucose metabolism.CytoJournal · 2025Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Brain vascular calcification is a prevalent age-related condition often accompanying neurodegenerative and neuroinflammatory diseases. The pathogenesis of large-vessel calcifications in peripheral tissue is well studied, but microvascular calcification in the brain remains poorly understood. Here, we report that elevated platelet-derived growth factor BB (PDGF-BB) from bone preosteoclasts contributed to cerebrovascular calcification in male mice. Aged male mice had higher serum PDGF-BB levels and a higher incidence of brain calcification compared with young mice, mainly in the thalamus. Transgenic mice with preosteoclast-specific Pdgfb overexpression exhibited elevated serum PDGF-BB levels and recapitulated age-associated thalamic calcification. Conversely, mice with preosteoclast-specific Pdgfb deletion displayed diminished age-associated thalamic calcification. In an ex vivo cerebral microvascular culture system, PDGF-BB dose-dependently promoted vascular calcification. Analysis of osteogenic gene array and single-cell RNA-Seq (scRNA-Seq) revealed that PDGF-BB upregulated multiple osteogenic differentiation genes and the phosphate transporter Slc20a1 in cerebral microvessels. Mechanistically, PDGF-BB stimulated the phosphorylation of its receptor PDGFRβ (p-PDGFRβ) and ERK (p-ERK), leading to the activation of RUNX2. This activation, in turn, induced the transcription of osteoblast differentiation genes in PCs and upregulated Slc20a1 in astrocytes. Thus, bone-derived PDGF-BB induced brain vascular calcification by activating the p-PDGFRβ/p-ERK/RUNX2 signaling cascade in cerebrovascular cells.
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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 Socratic graph.