Abstract
It establishes that inflammatory disorder of Th1 and Th17 cells promotes alveolar bone damage during periodontitis. It is proved that Galla Turcica has the function of anti-inflammation and immuno-modulation. We are going to uncover the potential effect of Galla Turcica in bone protection and T helper cell regulation during periodontitis. Experimental periodontitis animal models were chosen for the presented research. We recorded the bleeding on probing, tooth mobility, the alveolar bone resorption rate of target teeth, proportion of CD4 + T-bet + , CD4 + ror-γt + subsets in gingiva and peripheral blood, L-2, IFN-γ, IL-17, RANKL concentration in GCF and peripheral blood sera. In addition, we performed cell culture experiments to illustrate how Galla Turcica affects Th1 and Th17 cell differentiation and function. The proportion of CD4 + T-bet + , CD4 + ror-γt + subsets, and the mRNA level and concentration of IL-2, IFN-γ, IL-17, and RANKL in cultured cells or culture media were detected by real-time PCR and ELISA. We established that Galla Turcica administration not just remedies periodontal bleeding and tooth movement, but reduce alveolar bone resorption rate. Also, we find Galla Turcica administration reduced gingiva Th17 cell proportion and GCF RANKL, IL-17 concentration. In cell culture experiments, Galla Turcica decreases Th17 cell differentiation, and IL-17 transcription and secretion. Moreover, our study showed that Galla Turcica reduces STAT expression and phosphorylation, which prevent Th17 cell differentiation. The outcomes of our study highlight the functions and possible mechanisms of Galla Turcica engaged in periodontal inflammations, and reveal the considerable effect of Galla Turcica in regulating Th17 cell differentiation and their likely contribution to alveolar bone resorption during periodontitis.
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References
Ateeq H, Zia A, Husain Q, Khan MS, Ahmad M (2022) Effect of inflammation on bones in diabetic patients with periodontitis via RANKL/OPG system-a review. J Diabetes Metab Disord 21(1):1003–1009. https://doi.org/10.1007/s40200-021-00960-7.PMID:35673491;PMCID:PMC9167386
Ayyadurai VAS, Deonikar P (2021) Bioactive compounds in green tea may improve transplant tolerance: a computational systems biology analysis. Clin Nutr ESPEN 46:439–452. https://doi.org/10.1016/j.clnesp.2021.09.012. (Epub 2021 Sep 24 PMID: 34857232)
Brady A, McGeachy MJ (2023) Cloning of IL-12, a critical advance in Th1 and Th17 discovery. J Immunol 210(7):857–858. https://doi.org/10.4049/jimmunol.2300039. (PMID: 36947824)
Chen XT, Chen LL, Tan JY, Shi DH, Ke T, Lei LH (2016) Th17 and Th1 lymphocytes are correlated with chronic periodontitis. Immunol Invest 45(3):243–254. https://doi.org/10.3109/08820139.2016.1138967. (Epub 2016 Mar 28 PMID: 27019379)
Croes M, Kruyt MC, Groen WM, van Dorenmalen KMA, Dhert WJA, Öner FC, Alblas J (2018) Interleukin 17 enhances bone morphogenetic protein-2-induced ectopic bone formation. Sci Rep 8(1):7269. https://doi.org/10.1038/s41598-018-25564-9 (PMID:29740080; PMCID:PMC5940874)
Czesnikiewicz-Guzik M, Nosalski R, Mikolajczyk TP, Vidler F, Dohnal T, Dembowska E, Graham D, Harrison DG, Guzik TJ (2019). Th1-type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II-dependent hypertension and vascular dysfunction. Br J Pharmacol 176(12):1922–1931. https://doi.org/10.1111/bph.14536. Epub 2018 Dec 26. PMID: 30414380; PMCID: PMC6534780.
de Mello-Neto JM, Elangovan G, Ervolino E, Johnson NW, Gustafsson A, da Silva Figueredo CM (2023) Higher expression of Th1/Th2-related cytokines in the intestine of Wistar rats with ligature-induced periodontitis. J Periodontal Res 58(3):588–595. https://doi.org/10.1111/jre.13121. (Epub 2023 Mar 30 PMID: 36994797)
Gao J, Yang X, Yin W, Li M (2018) Gallnuts: a potential treasure in anticancer drug discovery. Evid Based Complement Alternat Med 2018:4930371. https://doi.org/10.1155/2018/4930371 (PMID:29785193; PMCID:PMC5896229)
Go J, Kim JE, Koh EK, Song SH, Kang HG, Lee YH, Kim HD, Hong JT, Hwang DY (2017) Hepatoprotective effect of gallotannin-enriched extract isolated from gall on hydrogen peroxide-induced cytotoxicity in HepG2 Cells. Pharmacogn Mag 13(Suppl 2):S294–S300. https://doi.org/10.4103/pm.pm_424_15. Epub 2017 Jul 11. PMID: 28808395; PMCID: PMC5538169.
Ikeuchi T, Moutsopoulos NM (2022) Osteoimmunology in periodontitis; a paradigm for Th17/IL-17 inflammatory bone loss. Bone 163:116500. https://doi.org/10.1016/j.bone.2022.116500. (Epub 2022 Jul 20 PMID: 35870792)
Ilango P, Kumar D, Mahalingam A, Thanigaimalai A, Reddy VK (2021) Evidence revealing the role of T cell regulators (Tregs) in periodontal diseases: a review. J Indian Soc Periodontol 25(4):278–282. https://doi.org/10.4103/jisp.jisp_308_20. Epub 2021 Jul 1. PMID: 34393396; PMCID: PMC8336777.
Kobpornchai P, Tiffney EA, Adisakwattana P, Flynn RJ (2021) Trichinella spiralis cystatin, TsCstN, modulates STAT4/IL-12 to specifically suppress IFN-γ production. Cell Immunol 362:104303. https://doi.org/10.1016/j.cellimm.2021.104303. (Epub 2021 Feb 4 PMID: 33611078)
Kotake S, Nanke Y, Mogi M, Kawamoto M, Furuya T, Yago T, Kobashigawa T, Togari A, Kamatani N (2005) IFN-gamma-producing human T cells directly induce osteoclastogenesis from human monocytes via the expression of RANKL. Eur J Immunol35(11):3353–3363. https://doi.org/10.1002/eji.200526141. PMID: 16220542.
Kwak SC, Cheon YH, Lee CH, Jun HY, Yoon KH, Lee MS, Kim JY (2020) Grape seed proanthocyanidin extract prevents bone loss via regulation of osteoclast differentiation, apoptosis, and proliferation. Nutrients 12(10):3164. https://doi.org/10.3390/nu12103164 (PMID:33081167; PMCID:PMC7602819)
Lai JH, Hsu YP, Yang CH, Chen YH, Liu CC, Chen SK (2022) Interferon-gamma regulates the levels of bone formation effectors in a stage-dependent manner. Mol Biol Rep 49(12):12007–12015. https://doi.org/10.1007/s11033-022-07993-y. (Epub 2022 Oct 23 PMID: 36273336)
Li X (2016) Oversea materia medica. Hubei Science and Technology Press, Shijiazhuang, China
Li J, Wang J, Song X, Li Z, Zhang Y, Lu H, Chen X (2022a) Effect of type 2 diabetes mellitus and periodontitis on the Th1/Th2 and Th17/Treg paradigm. Am J Dent 35(1):55–60 (PMID: 35316594)
Li YY, Lin YK, Li Y, Liu XH, Li DJ, Wang XL, Wang L, Zhu YZ, Yu M, Du MR (2022b) SCM-198 alleviates endometriosis by suppressing estrogen-ERα mediated differentiation and function of CD4+CD25+ Regulatory T Cells. Int J Biol Sci 18(5):1961–1973. https://doi.org/10.7150/ijbs.68224 (PMID:35342349; PMCID:PMC8935231)
Liu S, Li J, Feng LH (2023) Gallic acid regulates immune response in a mouse model of rheumatoid arthritis. Immun Inflamm Dis 11(2):e782. https://doi.org/10.1002/iid3.782 (PMID:36840490; PMCID:PMC9933205)
Lu Q, Chen H, Zhang J, Wang W, Cui Y, Liu J (2023) A study on the effect of host plants on Chinese gallnut morphogenesis. PLoS ONE 18(3):e0283464. https://doi.org/10.1371/journal.pone.0283464 (PMID:36947530; PMCID:PMC10032517)
Mardegan GP, Shibli JA, Roth LA, Faveri M, Giro G, Bastos MF (2023) Transforming growth factor-β, interleukin-17, and IL-23 gene expression profiles associated with human peri-implantitis. Clin Oral Implants Res 28(7):e10-e15. https://doi.org/10.1111/clr.12846. Epub 2016 Apr 7. PMID: 27062688.
McKinnon KM (2018) Flow cytometry: an overview. Curr Protoc Immunol 21;120:5.1.1–5.1.11. https://doi.org/10.1002/cpim.40. PMID: 29512141; PMCID: PMC5939936.
Medara N, Lenzo JC, Walsh KA, O’Brien-Simpson NM, Reynolds EC, Darby IB (2021) Peripheral T helper cell profiles during management of periodontitis. J Clin Periodontol 48(1):76–90. https://doi.org/10.1111/jcpe.13389. (Epub 2020 Nov 12 PMID: 33051896)
Moeintaghavi A, Arab HR, Rahim Rezaee SA, Naderi H, Shiezadeh F, Sadeghi S, Anvari N (2017) The effects of smoking on expression of IL-12 and IL-1β in gingival tissues of patients with chronic periodontitis. Open Dent J 11:595–602. https://doi.org/10.2174/1874210601711010595 (PMID:29299075; PMCID:PMC5725480)
Moon YM, Yoon BY, Her YM, Oh HJ, Lee JS, Kim KW, Lee SY, Woo YJ, Park KS, Park SH, Kim HY, Cho ML (2012) IL-32 and IL-17 interact and have the potential to aggravate osteoclastogenesis in rheumatoid arthritis. Arthritis Res Ther 14(6):R246. https://doi.org/10.1186/ar4089 (PMID:23148681; PMCID:PMC3674587)
Mysak J, Podzimek S, Sommerova P, Lyuya-Mi Y, Bartova J, Janatova T, Prochazkova J, Duskova J (2014) Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res, 476068. https://doi.org/10.1155/2014/476068. Epub 2014 Mar 25. PMID: 24741603; PMCID: PMC3984870.
Öngöz Dede F, Bozkurt Doğan Ş, Balli U, Durmuşlar MC, Avci B, Gülle K, Akpolat Ferah M (2021) The effect of ellagic acid on the repair process of periodontal defects related to experimental periodontitis in rats. J Appl Oral Sci 29:e20210160. https://doi.org/10.1590/1678-7757-2021-0160 (PMID:34586188; PMCID:PMC8483071)
Ren YY, Zhang XR, Li TN, Zeng YJ, Wang J, Huang QW (2021) Galla Chinensis, a Traditional Chinese Medicine: comprehensive review of botany, traditional uses, chemical composition, pharmacology and toxicology. J Ethnopharmacol 278:114247. https://doi.org/10.1016/j.jep.2021.114247. (Epub 2021 May 27 PMID: 34052353)
Singh C, Roy-Chowdhuri S (2016) Quantitative real-time PCR: recent advances. Methods Mol Biol 1392:161–176. https://doi.org/10.1007/978-1-4939-3360-0_15. (PMID: 26843055)
Slots J (2017) Periodontitis: facts, fallacies and the future. Periodontol 75(1):7–23. https://doi.org/10.1111/prd.12221. PMID: 28758294.
Song C, Yang X, Lei Y, Zhang Z, Smith W, Yan J, Kong L (2019) Evaluation of efficacy on RANKL induced osteoclast from RAW264.7 cells. J Cell Physiol 234(7):11969–11975. https://doi.org/10.1002/jcp.27852. Epub 2018 Dec 4. PMID: 30515780.
Tabatabaei MS, Ahmed M (2022) Enzyme-lnked immunosorbent assay (ELISA). Methods Mol Biol 2508:115–134. https://doi.org/10.1007/978-1-0716-2376-3_10. (PMID: 35737237)
Takayanagi H (2021) RANKL as the master regulator of osteoclast differentiation. J Bone Miner Metab 39(1):13–18. https://doi.org/10.1007/s00774-020-01191-1. (Epub 2021 Jan 1 PMID: 33385253)
Talwar A, Arun KV, Kumar TS, Clements J (2013) Plasticity of T helper cell subsets: implications in periodontal disease. J Indian Soc Periodontol 17(3):288–291. https://doi.org/10.4103/0972-124X.115637 (PMID:24049327; PMCID:PMC3768177)
Tan J, Dai A, Pan L, Zhang L, Wang Z, Ke T, Sun W, Wu Y, Ding PH, Chen L (2021) Inflamm-aging-related cytokines of IL-17 and IFN-γ accelerate osteoclastogenesis and periodontal destruction. J Immunol Res 2021:9919024. https://doi.org/10.1155/2021/9919024 (PMID:34395635; PMCID:PMC8357511)
Udagawa N, Koide M, Nakamura M, Nakamichi Y, Yamashita T, Uehara S, Kobayashi Y, Furuya Y, Yasuda H, Fukuda C, Tsuda E (2021) Osteoclast differentiation by RANKL and OPG signaling pathways. J Bone Miner Metab 39(1):19–26. https://doi.org/10.1007/s00774-020-01162-6. (Epub 2020 Oct 20 PMID: 33079279)
Wang Z, Wei Y, Lei L, Zhong J, Shen Y, Tan J, Xia M, Wu Y, Sun W, Chen L (2021) RANKL expression of primary osteoblasts is enhanced by an IL-17-mediated JAK2/STAT3 pathway through autophagy suppression. Connect Tissue Res 62(4):411–426. https://doi.org/10.1080/03008207.2020.1759562. (Epub 2020 May 5 PMID: 32370570)
Wang L, Liu S, Zhao Y, Liu D, Liu Y, Chen C, Karray S, Shi S, Jin Y (2015). Osteoblast-induced osteoclast apoptosis by fas ligand/FAS pathway is required for maintenance of bone mass. Cell Death Differ. 22(10):1654–64. https://doi.org/10.1038/cdd.2015.14. Epub 2015 Mar 6. PMID: 25744024; PMCID: PMC4563780.
Xu W, Zhou W, Wang H, Liang S (2020). Roles of Porphyromonas gingivalis and its virulence factors in periodontitis. Adv Protein Chem Struct Biol. 120:45–84. https://doi.org/10.1016/bs.apcsb.2019.12.001. Epub 2020 Jan 10. PMID: 32085888; PMCID: PMC8204362.
Zhang T, Chu J, Zhou X (2015) Anti-carious effects of Galla chinensis: a systematic review. Phytother Res 29(12):1837–1842. https://doi.org/10.1002/ptr.5444. (Epub 2015 Sep 1 PMID: 26331796)
Zhang B, Yang Y, Yi J, Zhao Z, Ye R (2021) Hyperglycemia modulates M1/M2 macrophage polarization via reactive oxygen species overproduction in ligature-induced periodontitis. J Periodontal Res 56(5):991–1005. https://doi.org/10.1111/jre.12912. (Epub 2021 Jun 30 PMID: 34190354)
Zhang P, Ye J, Dai J, Wang Y, Chen G, Hu J, Hu Q, Fei J (2022) Gallic acid inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss. Front Endocrinol (Lausanne) 13:963237. https://doi.org/10.3389/fendo.2022.963237 (PMID:36601012; PMCID:PMC9807166)
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This work was supported by grants from Industrial Technology Research and Development Special Project (2022C041-8), Province Jilin, China. The authors declare that they have no competing interests related to this study.
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Han, Y., Yu, C. & Yu, Y. Galla Turcica alleviates gingiva inflammation and alveolar bone resorption via regulating Th1/Th17 in a mouse model of periodontitis. ADV TRADIT MED (ADTM) (2024). https://doi.org/10.1007/s13596-024-00745-2
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DOI: https://doi.org/10.1007/s13596-024-00745-2