ArticleInflammation and regeneration2023
Enhancement of bone regeneration by coadministration of angiogenic and osteogenic factors using messenger RNA.
Article in Inflammation and regeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Heat shock protein-mediated remodeling of the bone immune microenvironment: mechanisms and precision therapeutic strategies for osteoporosis.Journal of translational medicine · 2026Review
- Mechanobiology of hypertrophic chondrocyte mineralization: Biomechanical regulation and therapeutic implications in skeletal disorders.Mechanobiology in medicine · 2026Review
- Nanomicelle-Based Multi-mRNA Delivery Promotes Cardiac Repair After Myocardial Infarction.Small science · 2026Article
- Protein-Encoding Chemically Modified mRNAs for Musculoskeletal Tissue Regeneration and Repair.Journal of functional biomaterials · 2026Review
- Donor age and sex program MSC secretome signaling: a quadrant framework for precision therapy.Stem cell research & therapy · 2026Article
- Biologics for bone regeneration: advances in cell, protein, gene, and mRNA therapies.Bone research · 2026Review
- hADMSC-YTZP seeding improves peri-implant bone repair through increased expression of BMP-2, ALP, and OPG.Scientific reports · 2025Article
- Cranial Bone Repair and Regeneration After Trauma: Forensic and Clinical Medico-Legal Consequences.Bioengineering (Basel, Switzerland) · 2025Review
- Molecular Determinants of Bone Plasticity Regeneration After Trauma: Forensic Consequences.International journal of molecular sciences · 2025Review
- ROS-responsive adaptive injectable hydrogel promoting inflammatory mastoid bone repair through efficient sterilization and regulating oxidative stress and macrophage phenotype.Materials today. Bio · 2025Article
- Using RNA therapeutics to promote healthy aging.Nature aging · 2025Review
- Revolutionizing Dentistry: Preclinical Insights and Future Applications of mRNA Vaccines in Dentistry-A Narrative Review.Dentistry journal · 2025Review
- Sex-specific divergences in the types and timing of infiltrating immune cells during the intervertebral disc acute injury response and their associations with degeneration.Osteoarthritis and cartilage · 2025Article
- Injectable Composite Hydrogel Stents for Bone Defect Management with Enhanced Osteogenesis and Angiogenesis.International journal of nanomedicine · 2025Article
- Advanced therapies in orthopaedics.EFORT open reviews · 2024Review
- β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model.Bioactive materials · 2024Article
- Vascular Damage and Repair - Are Small-Diameter Vascular Grafts Still the "Holy Grail" of Tissue Engineering?Physiological research · 2024Review
- Cholesterol-Bearing Polysaccharide-Based Nanogels for Development of Novel Immunotherapy and Regenerative Medicine.Gels (Basel, Switzerland) · 2024Review
- The Osteocyte with SB216763-Activated Canonical Wnt Signaling Constructs a Multifunctional 4D Intelligent Osteogenic Module.Biomolecules · 2024Article
- Treatment of chronic osteomyelitis with gradient release of DGEA and vancomycin hydrogel-microsphere system and its mechanism.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundBone defects remain a challenge today. In addition to osteogenic activation, the crucial role of angiogenesis has also gained attention. In particular, vascular endothelial growth factor (VEGF) is likely to play a significant role in bone regeneration, not only to restore blood supply but also to be directly involved in the osteogenic differentiation of mesenchymal stem cells. In this study, to produce additive angiogenic-osteogenic effects in the process of bone regeneration, VEGF and Runt-related transcription factor 2 (Runx2), an essential transcription factor for osteogenic differentiation, were coadministered with messenger RNAs (mRNAs) to bone defects in the rat mandible.
methodsThe mRNAs encoding VEGF or Runx2 were prepared via in vitro transcription (IVT). Osteogenic differentiation after mRNA transfection was evaluated using primary osteoblast-like cells, followed by an evaluation of the gene expression levels of osteogenic markers. The mRNAs were then administered to a bone defect prepared in the rat mandible using our original cationic polymer-based carrier, the polyplex nanomicelle. The bone regeneration was evaluated by micro-computerized tomography (μCT) imaging, and histologic analyses.
resultsOsteogenic markers such as osteocalcin (Ocn) and osteopontin (Opn) were significantly upregulated after mRNA transfection. VEGF mRNA was revealed to have a distinct osteoblastic function similar to that of Runx2 mRNA, and the combined use of the two mRNAs resulted in further upregulation of the markers. After in vivo administration into the bone defect, the two mRNAs induced significant enhancement of bone regeneration with increased bone mineralization. Histological analyses using antibodies against the Cluster of Differentiation 31 protein (CD31), alkaline phosphatase (ALP), or OCN revealed that the mRNAs induced the upregulation of osteogenic markers in the defect, together with increased vessel formation, leading to rapid bone formation.
conclusionsThese results demonstrate the feasibility of using mRNA medicines to introduce various therapeutic factors, including transcription factors, into target sites. This study provides valuable information for the development of mRNA therapeutics for tissue engineering.
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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.