Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions
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Published:2023-10-21
Issue:20
Volume:24
Page:15407
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Čolić Miodrag12, Miljuš Nataša3ORCID, Đokić Jelena4, Bekić Marina5, Krivokuća Aleksandra3, Tomić Sergej5ORCID, Radojević Dušan4, Radanović Marina2, Eraković Mile6, Ismaili Bashkim7, Škrbić Ranko3ORCID
Affiliation:
1. Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia 2. Medical Faculty Foča, University of East Sarajevo, 73300 Foča, Bosnia and Herzegovina 3. Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina 4. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia 5. Institute for the Application of Nuclear Energy, University of Belgrade, 11080 Belgrade, Serbia 6. Clinic for Stomatology, Medical Faculty of the Military Medical Academy, University of Defense, 11154 Belgrade, Serbia 7. Faculty of Dental Medicine, International Balkan University, 1000 Skopje, North Macedonia
Abstract
Pomegranate has shown a favorable effect on gingivitis/periodontitis, but the mechanisms involved are poorly understood. The aim of this study was to test the effect of pomegranate peel extract (PoPEx) on gingiva-derived mesenchymal stromal cells (GMSCs) under physiological and inflammatory conditions. GMSC lines from healthy (H) and periodontitis (P) gingiva (n = 3 of each) were established. The lines were treated with two non-toxic concentrations of PoPEX (low—10; high—40 µg/mL), with or without additional lipopolysaccharide (LPS) stimulation. Twenty-four genes in GMSCs involved in different functions were examined using real-time polymerase chain reaction (RT-PCR). PoPEx (mostly at higher concentrations) inhibited the basal expression of IL-6, MCP-1, GRO-α, RANTES, IP-10, HIF-1α, SDF-1, and HGF but increased the expression of IL-8, TLR3, TGF-β, TGF-β/LAP ratio, IDO-1, and IGFB4 genes in H-GMSCs. PoPEx increased IL-6, RANTES, MMP3, and BMP2 but inhibited TLR2 and GRO-α gene expression in P-GMSCs. LPS upregulated genes for proinflammatory cytokines and chemokines, tissue regeneration/repair (MMP3, IGFBP4, HGF), and immunomodulation (IP-10, RANTES, IDO-1, TLR3, COX-2), more strongly in P-GMSCs. PoPEx also potentiated most genes’ expression in LPS-stimulated P-GMSCs, including upregulation of osteoblastic genes (RUNX2, BMP2, COL1A1, and OPG), simultaneously inhibiting cell proliferation. In conclusion, the modulatory effects of PoPEx on gene expression in GMSCs are complex and dependent on applied concentrations, GMSC type, and LPS stimulation. Generally, the effect is more pronounced in inflammation-simulating conditions.
Funder
Ministry of Science, Technological Development and Innovation, Republic of Serbia University of Defense in Belgrade, Medical Faculty of the Military Medical Academy, Belgrade, Serbia University of East Sarajevo, Medical Faculty Foča, Foča, Bosnia and Herzegovina Medical Faculty Banja Luka, University of Banja Luka, Bosnia and Herzegovina
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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