ArticleSignal transduction and targeted therapy2024
Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss.
Article in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Yoda1-Functionalized Nanozymes Coordinate Piezo1 Activation and Mitochondrial Protection to Reprogram the Diabetic Osteoimmune Micromilieu and Promote Vascularized Bone Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cell Type-Specific Ferroptosis Regulatory Networks in the Bone Microenvironment: Implications for the Pathogenesis and Treatment of Osteoporosis.Traffic (Copenhagen, Denmark) · 2026Review
- Mesenchymal stem cell-derived small extracellular vesicles suppress pyroptosis by delivering miR-125a-5p to improve acute kidney injury in sepsis.Cell death discovery · 2026Article
- miR-423-5p-enriched small extracellular vesicles drive periodontal regeneration via Sfrp2+ cell expansion.Bioactive materials · 2026Article
- Molecular Investigation of the Effects of Two Antiepileptic Drugs (Valproic Acid and Levetiracetam) on Alveolar Bone Under Orthodontic Force.Medicina (Kaunas, Lithuania) · 2026Article
- Review
- Holistic regulation of the diabetic osteo-microenvironment via NIR-II nanocarriers with dual NO/pH responsiveness for enhanced bone regeneration.Bioactive materials · 2025Article
- Medication-Related Impacts on Pediatric Bone Health.Journal of the Pediatric Orthopaedic Society of North America · 2025Review
- Therapeutic targeting of STING-IL6/STAT3 axis to inhibit osteoclastic niche formation and breast cancer bone metastasis.Cell death discovery · 2025Article
- Antiseizure Medications and Bone Health.Neurology and therapy · 2025Review
- Progress of research on engineered extracellular vesicles from different sources for disease treatment.Histology and histopathology · 2025Review
- FNDC5/irisin-enriched sEVs conjugated with bone-targeting aptamer alleviate osteoporosis: a potential alternative to exercise.Journal of nanobiotechnology · 2025Article
- Article
- Next-generation probiotics and engineered BEVs for precision therapeutics in osteoporosis.Frontiers in nutrition · 2025Review
- Immune cells: the key mediator between the gut microbiota and osteoporosis.Frontiers in immunology · 2025Review
- Spatiotemporal application of small molecules in fracture healing.Biomaterials translational · 2025Review
- Enzalutamide inhibits PEX10 function and sensitizes prostate cancer cells to ROS activators.Cell death & disease · 2024Article
- Cinobufagin Suppresses Lipid Peroxidation and Inflammation in Osteoporotic Mice by Promoting the Delivery of miR-3102-5p by Macrophage-Derived Exosomes.International journal of nanomedicine · 2024Article
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Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical role and underlying mechanisms of valproic acid (VPA) on bone homeostasis remain controversial. Herein, we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density (BMD) in both patients and mice. This effect was attributed to VPA-induced elevation in osteoclast formation and activity. Through RNA-sequencing, we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro, and further, a marked upregulation of mature miR-6359 (miR-6359) in vivo was demonstrated using quantitative real-time PCR (qRT-PCR) and miR-6359 fluorescent in situ hybridization (miR-6359-FISH). Specifically, the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils, T lymphocytes, monocytes and bone marrow-derived mesenchymal stem cells (BMSCs) following VPA stimulation, which influenced osteoclast differentiation and bone-resorptive activity. Additionally, VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species (ROS) production by silencing the SIRT3 protein expression, followed by activation of the MAPK signaling pathway, which enhanced osteoclast formation and activity, thereby accelerating bone loss. Currently, there are no medications that can effectively treat VPA-induced bone loss. Therefore, we constructed engineered small extracellular vesicles (E-sEVs) targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif (CGGGAGC) in the 3'-end of the anti-miR-6359 sequence. We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss, but not on ovariectomy (OVX) and glucocorticoid-induced osteoporotic models, deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.
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