ArticleJournal of translational medicine2024
Inhibition of soluble epoxide hydrolase enhances the dentin-pulp complex regeneration mediated by crosstalk between vascular endothelial cells and dental pulp stem cells.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Soluble Epoxide Hydrolase Inhibition Regulates Septoclast Activity to Promote Long Bone Growth and Fracture Healing by Enhancing Endothelial-to-Mesenchymal Notch Signalling.Cell proliferation · 2026Article
- Exposure to polylactic acid microplastics during puberty increases the risk of skeletal dysplasia by disrupting arachidonic acid metabolism in osteoblasts.Particle and fibre toxicology · 2026Article
- An immunomodulatory decellularized pulp matrix hydrogel promotes vascularized dental pulp regeneration through angiogenic-odontogenic coupling.Regenerative biomaterials · 2026Article
- CGRP-mediated neuro-vascular-pulp cell crosstalk is essential for dental pulp repair.Frontiers in cell and developmental biology · 2026Article
- [Research Progress on the Role and Regulatory Mechanisms of Lipid Metabolism in the Osteogenic/Odontogenic Differentiation of Dental Stem Cells].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Review
- Mechanistic insights into dental stem cells-derived exosomes in regenerative endodontics.International endodontic journal · 2025Review
- Targeted soluble epoxide hydrolase inhibits M1 macrophage polarization to improve cartilage injury in temporomandibular joint osteoarthritis.Journal of translational medicine · 2025Article
- METTL3 promotes immature dental pulp stem cells-induced angiogenesis by regulating ETS1 mRNA stability in an mOdontology · 2025Article
- Strontium-doped hydroxyapatite microspheres loaded with iloprost promote dentin-pulp complex regeneration.Frontiers in bioengineering and biotechnology · 2025Article
- Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain.International journal of molecular sciences · 2024Article
- Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration.Open life sciences · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRevascularization and restoration of normal pulp-dentin complex are important for tissue-engineered pulp regeneration. Recently, a unique periodontal tip-like endothelial cells subtype (POTCs) specialized to dentinogenesis was identified. We have confirmed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor targeting epoxyeicosatrienoic acids (EETs) metabolism, promotes bone growth and regeneration by angiogenesis and osteogenesis coupling. We hypothesized that TPPU could also promote revascularization and induce POTCs to contribute to pulp-dentin complex regeneration. Here, we in vitro and in vivo characterized the potential effect of TPPU on the coupling of angiogenesis and odontogenesis and investigated the relevant mechanism, providing new ideas for pulp-dentin regeneration by targeting sEH.
methodsIn vitro effects of TPPU on the proliferation, migration, and angiogenesis of dental pulp stem cells (DPSCs), human umbilical vein endothelial cells (HUVECs) and cocultured DPSCs and HUVECs were detected using cell counting kit 8 (CCK8) assay, wound healing, transwell, tube formation and RT-qPCR. In vivo, Matrigel plug assay was performed to outline the roles of TPPU in revascularization and survival of grafts. Then we characterized the VEGFR2 + POTCs around odontoblast layer in the molar of pups from C57BL/6 female mice gavaged with TPPU. Finally, the root segments with DPSCs mixed with Matrigel were implanted subcutaneously in BALB/c nude mice treated with TPPU and the root grafts were isolated for histological staining.
resultsIn vitro, TPPU significantly promoted the migration and tube formation capability of cocultured DPSCs and HUVECs. ALP and ARS staining and RT-qPCR showed that TPPU promoted the osteogenic and odontogenic differentiation of cultured cells, treatment with an anti-TGF-β blocking antibody abrogated this effect. Knockdown of HIF-1α in HUVECs significantly reversed the effect of TPPU on the expression of angiogenesis, osteogenesis and odontogenesis-related genes in cocultured cells. Matrigel plug assay showed that TPPU increased VEGF/VEGFR2-expressed cells in transplanted grafts. TPPU contributed to angiogenic-odontogenic coupling featured by increased VEGFR2 + POTCs and odontoblast maturation during early dentinogenesis in molar of newborn pups from C57BL/6 female mice gavaged with TPPU. TPPU induced more dental pulp-like tissue with more vessels and collagen fibers in transplanted root segment.
conclusionsTPPU promotes revascularization of dental pulp regeneration by enhancing migration and angiogenesis of HUVECs, and improves odontogenic differentiation of DPSCs by TGF-β. TPPU boosts the angiogenic-odontogenic coupling by enhancing VEGFR2 + POTCs meditated odontoblast maturation partly via upregulating HIF-1α, which contributes to increasing pulp-dentin complex for tissue-engineered pulp regeneration.
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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.