ArticleMedical science monitor : international medical journal of experimental and clinical research2019
Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway.
Article in Medical science monitor : international medical journal of experimental and clinical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- In Vitro Cytotoxicity of Antiresorptive and Antiangiogenic Compounds on Oral Tissues Contributing to MRONJ: Systematic Review.Biomolecules · 2023Pooled it
- New Immunological Insights into Bisphosphonate-Related Osteonecrosis of the Jaw: A Multidimensional Reappraisal from Molecular Switches to Clinical Phenotypes.Current issues in molecular biology · 2026Review
- Micro/nano-structured titanium surfaces promote endothelial responses and angiogenic activity under zoledronic acid exposure.BMC oral health · 2026Article
- Osteoclast-derived exosomes promote medication-related osteonecrosis of the jaw by delivering glycoRNA to disrupt the blood-lymphatic vascular network.Journal of dental sciences · 2026Article
- The PI3K/AKT/mTOR Pathway and Oral Diseases: A Bibliometric Analysis From 2008 to 2025.Clinical and experimental dental research · 2025Article
- The Cellular and Mitochondrial Consequences of Mevalonate Pathway Inhibition by Nitrogen-Containing Bisphosphonates: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway.Open medicine (Warsaw, Poland) · 2024Article
- The EGF/EGFR axis and its downstream signaling pathways regulate the motility and proliferation of cultured oral keratinocytes.FEBS open bio · 2023Article
- Inhibitory potency of the nettle lectin on neovascularization: a biomolecule for carbohydrate-mediated targeting of angiogenesis.Molecular biology reports · 2023Article
- Zoledronic acid affects the process ofFrontiers in cellular and infection microbiology · 2023Article
- Interleukin-17 plays a role in dental pulp inflammation mediated by zoledronic acid: a mechanism unrelated to the Th17 immune response?Journal of applied oral science : revista FOB · 2023Article
- Innovative Concepts and Recent Breakthrough for Engineered Graft and Constructs for Bone Regeneration: A Literature Systematic Review.Materials (Basel, Switzerland) · 2022Review
- Medication-Related Osteonecrosis of the Jaws Initiated by Zoledronic Acid and Potential Pathophysiology.Dentistry journal · 2021Review
- Mechanism, prevention, and treatment for medication-related osteonecrosis of the jaws.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021Review
- Exosome-derived miR-196b-5p facilitates intercellular interaction in infantile hemangioma via down-regulating CDKN1B.Annals of translational medicine · 2021Article
- The Role of the Immune Response in the Development of Medication-Related Osteonecrosis of the Jaw.Frontiers in immunology · 2021Review
- Biphasic Effect of Pirfenidone on Angiogenesis.Frontiers in pharmacology · 2021Article
- A Review Into the Effects of Pamidronic Acid and Zoledronic Acid on the Oral Mucosa in Medication-Related Osteonecrosis of the Jaw.Frontiers in oral health · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND Medication-related osteonecrosis of the jaw (MRONJ) is due to the direct effects of drug toxicity and the effects on angiogenesis. The aims of this study were to evaluate the effects of treatment with the bisphosphonate, zoledronic acid, on human oral keratinocytes (HOKs) and human umbilical vein endothelial cells (HUVECs) in vitro, and whether epidermal growth factor (EGF) could alter these effects. MATERIAL AND METHODS HOKs and HUVECs were incubated with zoledronic acid or EGF. Cell viability was assessed by the cell counting kit-8 (CCK-8), cell apoptosis was studied using Annexin-V conjugated to fluorescein isothiocyanate (FITC). Angiogenesis was studied by observing HUVEC tube formation and cell migrations using a transwell assay. A scratch wound assay investigated cell migration of HOKs. Western blot measured expression levels of phosphorylated epidermal growth factor receptor (EGFR), Akt, phosphoinositide 3-kinase (PI3K), the mechanistic target of rapamycin (mTOR), and endothelial nitric oxide synthase (eNOS). RESULTS Zoledronic acid treatment (5 µmol/L) significantly inhibited cell viability and cell migration of HOKs and HUVECs and angiogenesis of HUVECS (P<0.05); EGF partially reversed these effects (P<0.05). Zoledronic acid treatment of HOKs and HUVECs had no significant effects on apoptosis (P>0.05), but significantly reduced expression levels of p-EGFR, p-Akt, p-PI3K, p-mTOR), and p-eNOS (P<0.05); EGF partially reversed these effects and increased the expression levels (P<0.05). CONCLUSIONS EGF partially reversed the effects of the bisphosphonate, zoledronic acid, on HOKs and HUVECs in vitro via the EGFR/Akt/PI3K signaling pathway. Further studies are required to determine the effects of EGF on MRONJ including bisphosphonate-related osteonecrosis of the jaw.
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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.