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 PathwayQizhang Wang1ABCDEF, Jiyuan Liu1ADFG, Ting Guo1BCD, Dazhong Liu2FG, Jian Pan1AG*
Med Sci Monit 2019; 25:700-710
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, Proto-Oncogene Proteins c-akt, Receptor, Epidermal Growth Factor, Apoptosis, Cell Movement, Cell Proliferation, Cell Survival, ErbB receptors, Human Umbilical Vein Endothelial Cells, Neovascularization, Pathologic, Neovascularization, Physiologic, Nitric Oxide Synthase Type III, Phosphatidylinositol 3-Kinases, Signal Transduction, zoledronic acid
01 May 2022 : EditorialEditorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19
Med Sci Monit 2022; 28:e937048
04 May 2022 : Clinical ResearchEffects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936069
27 May 2022 : Clinical ResearchFactors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)
Med Sci Monit 2022; 28:e936547
25 May 2022 : Review articleNarrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of Dislocation
Med Sci Monit In Press; DOI: 10.12659/MSM.935665
24 May 2022 : Clinical ResearchRemimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936580
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
01 Nov 2020 : Review articleLong-Term Respiratory and Neurological Sequelae of COVID-19
Med Sci Monit 2020; 26:e928996