ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Engineering a targeted and safe bone anabolic gene therapy to treat osteoporosis in alveolar bone loss.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Bone aging: a paradigm of multiscale degeneration and targeted rejuvenation.Bone research · 2026Review
- Senescent BMSC-Derived Thbs1 Drives Inflammaging and Impairs Bone Regeneration by Suppressing PINK1/Parkin-Mediated Mitophagy in Macrophages.Aging cell · 2026Article
- Zinc and metformin co-functionalized polyetheretherketone: A novel dental implant material tailored for the elderly.Journal of advanced research · 2026Article
- MicroRNA-based targeting strategies enable AAV-mediated, tissue-selective gene expression in adipose tissue and skeletal muscle of mice.Molecular therapy. Advances · 2026Article
- Knockdown of GCNT2 promoted osteoblast differentiation by activating PI3K/AKT/mTOR pathway in osteoblasts.Scientific reports · 2025Article
- Recent developments in translational imaging of in vivo gene therapy outcomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- miR-374-5p inhibits osteogenesis by targeting PTEN/PI3K/AKT signaling pathway.Journal of orthopaedic surgery and research · 2025Article
- Comparative analysis of dental-derived stem cells and alternative stem cell sources: properties and regenerative functions.Frontiers in bioengineering and biotechnology · 2025Review
- Osteocytes: master orchestrators of skeletal homeostasis, remodeling, and osteoporosis pathogenesis.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
Alveolar bone loss in elderly populations is highly prevalent and increases the risk of tooth loss, gum disease susceptibility, and facial deformity. Unfortunately, there are very limited treatment options available. Here, we developed a bone-targeted gene therapy that reverses alveolar bone loss in patients with osteoporosis by targeting the adaptor protein Schnurri-3 (SHN3). SHN3 is a promising therapeutic target for alveolar bone regeneration, because SHN3 expression is elevated in the mandible tissues of humans and mice with osteoporosis while deletion of SHN3 in mice greatly increases alveolar bone and tooth dentin mass. We used a bone-targeted recombinant adeno-associated virus (rAAV) carrying an artificial microRNA (miRNA) that silences SHN3 expression to restore alveolar bone loss in mouse models of both postmenopausal and senile osteoporosis by enhancing WNT signaling and osteoblast function. In addition, rAAV-mediated silencing of SHN3 enhanced bone formation and collagen production of human skeletal organoids in xenograft mice. Finally, rAAV expression in the mandible was tightly controlled via liver- and heart-specific miRNA-mediated repression or via a vibration-inducible mechanism. Collectively, our results demonstrate that AAV-based bone anabolic gene therapy is a promising strategy to treat alveolar bone loss in osteoporosis.
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