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Protective Effects of Ursolic Acid on Osteoblastic Differentiation via Activation of IER3/Nrf2
J Dent Hyg Sci 2019;19:198-204
Published online September 30, 2019;
© 2019 Korean Society of Dental Hygiene Science.

Sang-im Lee

Department of Dental Hygiene, College of Health Sciences, Dankook University, Cheonan 31116, Korea
Correspondence to: Sang-im Lee,
Department of Dental Hygiene, College of Health Sciences, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, Korea
Tel: +82-41-550-1492, E-mail:
Received August 6, 2019; Revised August 28, 2019; Accepted September 3, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background:Oxidative stress is a known to be associated with in the pathogenesis of many inflammatory diseases, including periodontitis. Ursolic acid is a pentacyclic triterpenoid with has antimicrobial, antioxidative, and anticancer properties. However, the role of ursolic acid in the regulating of osteogenesis remains undetermined. This study was aimed to elucidate the crucial osteogenic effects of ursolic acid and its ability to inhibit oxidative stress by targeting the immediate early response 3 (IER3)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
Methods:Cell proliferation was determined using water-soluble tetrazolium salt assay, cell differentiation was evaluated by alkaline phosphatase (ALP) activity, and formation of calcium nodules was detected using alizarin red S stain. Generation of reactive oxygen species (ROS) was determined using by DCFH-DA fluorescence dye in hydrogen peroxide (H2O2)-treated MG-63 cells. Expression levels of IER3, Nrf2, and heme oxygenase-1 (HO-1) were analyzed using western blot analysis.
Results:Our results showed that ursolic acid up-regulated the proliferation of osteoblasts without any cytotoxic effects, and promoted ALP activity and mineralization. H2O2-induced ROS generation was found to be significantly inhibited on treatment with ursolic acid. Furthermore, in H2O2-treated cells, the expression of the early response genes: IER3, Nrf2, and Nrf2-related phase II enzyme (HO-1) was enhanced in the presence of ursolic acid.
Conclusion:The key findings of the present study elucidate the protective effects of ursolic acid against oxidative stress conditions in osteoblasts via the IER3/Nrf2 pathway. Thus, ursolic acid may be developed as a preventative and therapeutic agent for mineral homeostasis and inflammatory diseases caused due to oxidative injury.
Keywords : Immediate early response 3 protein, NF-E2-related factor 2, Osteoblast, Oxidative stress, Periodontal disease

September 2019, 19 (3)
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