Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions
Authors
Čolić, MiodragMiljuš, Nataša
Đokić, Jelena
Bekić, Marina
Krivokuća, Aleksandra
Tomić, Sergej
Radojević, Dušan
Radanović, Marina
Eraković, Mile
Ismaili, Bashkim
Škrbić, Ranko
Article (Published version)
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Show full item recordAbstract
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 expressio...n 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.
Keywords:
gene expression / gingiva / mesenchymal stromal cells / periodontitis / pomegranateSource:
International Journal of Molecular Sciences, 2023, 24, 20, 15407-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200019 (University of Belgrade, Institute for the Application of Nuclear Energy - INEP) (RS-MESTD-inst-2020-200019)
- University of Defense in Belgrade, Medical Faculty of the Military Medical Academy, Belgrade, Serbia (project MFVMA/03/20-22)
- University of East Sarajevo, Medical Faculty Foˇca, Foˇca, Bosnia and Herzegovina, (project UIS/MFF: I.1.20-22) and Medical Faculty Banja Luka, University of Banja Luka, Bosnia and Herzegovina
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Čolić, Miodrag AU - Miljuš, Nataša AU - Đokić, Jelena AU - Bekić, Marina AU - Krivokuća, Aleksandra AU - Tomić, Sergej AU - Radojević, Dušan AU - Radanović, Marina AU - Eraković, Mile AU - Ismaili, Bashkim AU - Škrbić, Ranko PY - 2023 UR - https://www.mdpi.com/1422-0067/24/20/15407 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2167 AB - 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. T2 - International Journal of Molecular Sciences T2 - International Journal of Molecular Sciences T1 - Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions IS - 20 SP - 15407 VL - 24 DO - 10.3390/ijms242015407 ER -
@article{ author = "Čolić, Miodrag and Miljuš, Nataša and Đokić, Jelena and Bekić, Marina and Krivokuća, Aleksandra and Tomić, Sergej and Radojević, Dušan and Radanović, Marina and Eraković, Mile and Ismaili, Bashkim and Škrbić, Ranko", year = "2023", 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.", journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences", title = "Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions", number = "20", pages = "15407", volume = "24", doi = "10.3390/ijms242015407" }
Čolić, M., Miljuš, N., Đokić, J., Bekić, M., Krivokuća, A., Tomić, S., Radojević, D., Radanović, M., Eraković, M., Ismaili, B.,& Škrbić, R.. (2023). Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions. in International Journal of Molecular Sciences, 24(20), 15407. https://doi.org/10.3390/ijms242015407
Čolić M, Miljuš N, Đokić J, Bekić M, Krivokuća A, Tomić S, Radojević D, Radanović M, Eraković M, Ismaili B, Škrbić R. Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions. in International Journal of Molecular Sciences. 2023;24(20):15407. doi:10.3390/ijms242015407 .
Čolić, Miodrag, Miljuš, Nataša, Đokić, Jelena, Bekić, Marina, Krivokuća, Aleksandra, Tomić, Sergej, Radojević, Dušan, Radanović, Marina, Eraković, Mile, Ismaili, Bashkim, Škrbić, Ranko, "Pomegranate Peel Extract Differently Modulates Gene Expression in Gingiva-Derived Mesenchymal Stromal Cells under Physiological and Inflammatory Conditions" in International Journal of Molecular Sciences, 24, no. 20 (2023):15407, https://doi.org/10.3390/ijms242015407 . .