24 January 2019 : Laboratory Research
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
Qizhang Wang1ABCDEF, Jiyuan Liu1ADFG, Ting Guo1BCD, Dazhong Liu2FG, Jian Pan1AG*DOI: 10.12659/MSM.911579
Med Sci Monit 2019; 25:700-710
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.
Keywords: Bisphosphonate-Associated Osteonecrosis of the Jaw, endothelial cells, Epidermal Growth Factor, Keratinocytes, Receptor, Epidermal Growth Factor, ErbB receptors, Neovascularization, Physiologic, Nitric Oxide Synthase Type III, zoledronic acid
Editorial
01 February 2025 : Editorial
Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-SmokersDOI: 10.12659/MSM.948255
Med Sci Monit 2025; 31:e948255
In Press
Clinical Research
Pre- and Post-Surgical MRI Analysis of Levator Ani in Pelvic Organ Prolapse Patients: A Single-Center StudyMed Sci Monit In Press; DOI: 10.12659/MSM.945993
Clinical Research
Comparative Impact of Kinesio Taping and Post-Isometric Muscle Relaxation on Pain and Myofascial Mechanics ...Med Sci Monit In Press; DOI: 10.12659/MSM.945376
Clinical Research
Surgical Efficacy in Varicocele Ligation with Ephedrine-Assisted Blood Pressure ControlMed Sci Monit In Press; DOI: 10.12659/MSM.946234
Clinical Research
Retrospective Study to Compare Injury Patterns and Associations in 170 Patients Following Electric Scooter ...Med Sci Monit In Press; DOI: 10.12659/MSM.947155
Most Viewed Current Articles
17 Jan 2024 : Review article 6,968,277
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research 701,791
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Mar 2024 : Editorial 25,442
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...DOI :10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
28 Jan 2024 : Review article 20,020
A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and FutureDOI :10.12659/MSM.943912
Med Sci Monit 2024; 30:e943912