Int J Stomatol

Int J Stomatol ›› 2023, Vol. 50 ›› Issue (6): 661-668.doi: 10.7518/gjkq.2023082

• Original Articles • Previous Articles     Next Articles

Relationship between periodontitis and ferroptosis based on bioinformatics analysis

Luo Xiaojie1,2(),Wang Dexu1,2,Chen Xiaotao2()   

  1. 1.Dept. of Stomatology, Xinjiang Medical University, Urumqi 830000, China
    2.Dept. of Stomatology, Xinjiang Uygur Autonomous Region People’s Hospital, Urumqi 830000, China
  • Received:2023-02-18 Revised:2023-06-06 Online:2023-11-01 Published:2023-10-24
  • Contact: Xiaotao Chen E-mail:453540314@qq.com;xiaotaochen@163.com
  • Supported by:
    National Natural Science Foundation of China(82260195);Xinjiang Uygur Autonomous Region Regional Collaborative Innovation Special Fund(2021E02071)

RichHTML

18

PDF (PC)

933

Abstract:

Objective Bioinformatics methods were used to investigate the correlation between periodontitis and ferroptosis. Methods Dataset GS16134 was downloaded from the GEO database, and the driver and suppressor genes of ferroptosis were downloaded from the ferroptosis database (FerrDb). R soft was used to standardize the data, and the “limma” package was used to screen for differentially expressed genes in periodontitis (P<0.05). GO and KEGG analyses were conducted to analyze the differentially expressed genes and identify their main functions and pathways. Protein interaction network was used to screen for key mRNAs. Results Fifty differentially expressed ferroptosis regulatory genes were screened in periodontitis gingival tissue samples and healthy gingival tissue samples. Results of GO function and KEGG pathway analyses showed that the differentially expressed genes mainly participated in the oxidative stress reaction, and they were mainly concentrated in the ferroptosis pathway. Conclusion Ferroptosis regulatory genes were differentially expressed in periodontitis tissue samples, and these genes primarily functioned in the oxidative stress and iron metabolism pathways, indicating a correlation between the two. Ferroptosis may affect inflammation and even bone remodeling of alveolar bone through lipid peroxidation, as well as abnormal iron metabolism. This study provides new insights into the mechanism of periodontitis development.

Key words: periodontitis, ferroptosis, bioinformation

CLC Number: 

  • R 781.4+2

TrendMD: 

Fig 1

Differential expression of iron death regulatory genes in inflammatory and healthy samples"

Fig 2

GO analysis results of differentially expressed genes"

Tab 1

Results of differentially expressed genes"

GO IDGO TermGene ID数目
GO:006979氧化应激反应ALOX5/SLC7A11/TLR4/NFE2L2/PRDX6/EPAS1/DUOX1/MYB/CYBB/DUOX2/NQO1/GCLC/HMOX1/GCH1/MAP1LC3A15
GO:0062197细胞化学应激反应ALOX5/SLC7A11/TLR4/NFE2L2/PRDX6/EPAS1/MYB/CYBB/ATM/NQO1/HMOX1/GCH1/MAP1LC3A13
GO:0034599细胞氧化应激反应ALOX5/SLC7A11/TLR4/NFE2L2/PRDX6/EPAS1/MYB/CYBB/NQO1/HMOX1/GCH1/MAP1LC3A12

Fig 3

KEGG pathway analysis results of differentially expressed genes"

Tab 2

Pathway analysis results of differentially expressed genes"

Pathway ID描述Gene ID数目
hsa04216铁死亡通路FTH1/SLC7A11/SAT1/CYBB/VDAC2/NCOA4/ACSL4/SLC40A1/SLC3A2/GCLC/HMOX1/ACSL3/MAP1LC3A13
hsa04621NOD样受体信号通路TLR4/CYBB/VDAC2/PANX1/ATG16L1/MAPK14/MAP1LC3A7
hsa04140自噬通路ATG3/ATG16L1/ULK1/WIPI1/HRAS/MAP1LC3A6

Fig 4

Main roles of some differential genes in KEGG iron death pathway"

Fig 5

PPI network of differentially expressed genes constructed by Cytoscape"

Fig 6

15 key genes obtained through the ECODE plugin in Cytoscape"

"

1 Kassebaum NJ, Bernabé E, Dahiya M, et al. Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression[J]. J Dent Res, 2014, 93(11): 1045-1053.
2 Pihlstrom BL, Michalowicz BS, Johnson NW. Pe-riodontal diseases[J]. Lancet, 2005, 366(9499): 1809-1820.
3 Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death[J]. Cell, 2012, 149(5): 1060-1072.
4 Sun YT, Chen P, Zhai BT, et al. The emerging role of ferroptosis in inflammation[J]. Biomed Pharmacother, 2020, 127: 110108.
5 Papapanou PN, Behle JH, Kebschull M, et al. Subgingival bacterial colonization profiles correlate with gingival tissue gene expression[J]. BMC Microbiol, 2009, 9: 221.
6 Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA-sequen-cing and microarray studies[J]. Nucleic Acids Res, 2015, 43(7): e47.
7 Cai W, Li H, Zhang Y, et al. Identification of key biomarkers and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis[J]. PeerJ, 2020, 8: e8390.
8 Sczepanik FSC, Grossi ML, Casati M, et al. Perio-dontitis is an inflammatory disease of oxidative stress: we should treat it that way[J]. Periodontol 2000, 2020, 84(1): 45-68.
9 Chen MM, Cai WJ, Zhao SF, et al. Oxidative stress-related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: a syste-matic review and meta-analysis[J]. J Clin Periodontol, 2019, 46(6): 608-622.
10 Wang Y, Andrukhov O, Rausch-Fan X. Oxidative stress and antioxidant system in periodontitis[J]. Front Physiol, 2017, 8: 910.
11 Cao JY, Dixon SJ. Mechanisms of ferroptosis[J]. Cell Mol Life Sci, 2016, 73(11/12): 2195-2209.
12 Koppula P, Zhuang L, Gan BY. Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy[J]. Protein Cell, 2021, 12(8): 599-620.
13 Yang WS, Stockwell BR. Ferroptosis: death by lipid peroxidation[J]. Trends Cell Biol, 2016, 26(3): 165-176.
14 李春燕, 孙传政, 宋鑫. 肿瘤细胞死亡的一种新形式: 铁死亡[J]. 中国生物化学与分子生物学报, 2019, 35(11): 1208-1214.
Li CY, Sun CZ, Song X. A new form of tumor cell death: ferroptosis[J]. Chin J Biochem Mol Biol, 2019, 35(11): 1208-1214.
15 Gluschko A, Farid A, Herb M, et al. Macrophages target Listeria monocytogenes by two discrete non-canonical autophagy pathways[J]. Autophagy, 2022, 18(5): 1090-1107.
16 Chen HY, Sun Q, Zhang CG, et al. Identification and validation of CYBB, CD86, and C3AR1 as the key genes related to macrophage infiltration of gastric cancer[J]. Front Mol Biosci, 2021, 8: 756085.
17 Galaris D, Barbouti A, Pantopoulos K. Iron homeostasis and oxidative stress: an intimate relationship[J]. Biochim Biophys Acta Mol Cell Res, 2019, 1866(12): 118535.
18 Brown CW, Amante JJ, Chhoy P, et al. Prominin2 drives ferroptosis resistance by stimulating iron export[J]. Dev Cell, 2019, 51(5): 575-586.e4.
19 Kuang YB, Wang Q. Iron and lung cancer[J]. Cancer Lett, 2019, 464: 56-61.
20 Hou W, Xie YC, Song XX, et al. Autophagy promotes ferroptosis by degradation of ferritin[J]. Autophagy, 2016, 12(8): 1425-1428.
21 Guo W, Zhao YH, Li HX, et al. NCOA4-mediated ferritinophagy promoted inflammatory responses in periodontitis[J]. J Periodontal Res, 2021, 56(3): 523-534.
22 Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer[J]. Nat Rev Cancer, 2017, 17(9): 528-542.
23 Ni S, Yuan Y, Qian Z, et al. Hypoxia inhibits RANKL-induced ferritinophagy and protects osteoclasts from ferroptosis[J]. Free Radic Biol Med, 2021, 169: 271-282.
24 Jin CY, Zhang P, Zhang M, et al. Inhibition of SLC7A11 by sulfasalazine enhances osteogenic differentiation of mesenchymal stem cells by modula-ting BMP2/4 expression and suppresses bone loss in ovariectomized mice[J]. J Bone Miner Res, 2017, 32(3): 508-521.
25 Han B, Geng H, Liu L, et al. GSH attenuates RANKL-induced osteoclast formation in vitro and LPS-induced bone loss in vivo [J]. Biomed Pharmacother, 2020, 128: 110305.
26 Huynh H, Wan YH. mTORC1 impedes osteoclast differentiation via calcineurin and NFATc1 [J]. Commun Biol, 2018, 1: 29.
27 Fujita H, Ochi M, Ono M, et al. Glutathione accele-rates osteoclast differentiation and inflammatory bone destruction[J]. Free Radic Res, 2019, 53(2): 226-236.
28 Lee DE, Kim JH, Choi SH, et al. Periodontitis mainly increases osteoclast formation via enhancing the differentiation of quiescent osteoclast precursors into osteoclasts[J]. J Periodontal Res, 2015, 50(2): 256-264.
29 Agidigbi TS, Kang IS, Kim C. Inhibition of MEK/ERK upregulates GSH production and increases RANKL-induced osteoclast differentiation in RAW 264.7 cells[J]. Free Radic Res, 2020, 54(11/12): 894-905.
30 Ledesma-Colunga MG, Weidner H, Vujic Spasic M, et al. Shaping the bone through iron and iron-related proteins[J]. Semin Hematol, 2021, 58(3): 188-200.
[1] Fu Yu, He Wei, Huang Lan. Ferroptosis and its implication in oral diseases [J]. Int J Stomatol, 2024, 51(1): 36-44.
[2] Huang Yuanhong,Peng Xian,Zhou Xuedong.. Progress in research into the effect of Rhizoma Drynariae on the treatment of bone-related diseases in the oral cavity [J]. Int J Stomatol, 2023, 50(6): 679-685.
[3] Hu Jia,Wang Xiuqing,Lu Guoying,Huang Xiaojing.. Regenerative endodontic procedures for permanent tooth with immature apices in adult patients [J]. Int J Stomatol, 2023, 50(6): 686-695.
[4] Gong Meiling,Cheng Xingqun,Wu Hongkun.. Research progress on the correlation between Parkinson’s disease and periodontitis [J]. Int J Stomatol, 2023, 50(5): 587-593.
[5] Xu Zhibo,Meng Xiuping.. Research progress on mechanism of Enterococcus faecalis escaping host immune defense [J]. Int J Stomatol, 2023, 50(5): 613-617.
[6] Sun Jia,Han Ye,Hou Jianxia. Research progress on the role of interleukin-6-hepcidin signal axis in regulating the pathogenesis of periodontitis-associated anemia [J]. Int J Stomatol, 2023, 50(3): 329-334.
[7] Liang Zhiying,Zhao Yuanxi,Zhu Jiani,Su Qin.. Retrospective analysis of clinical data of 288 cases of endodontic microsurgery on anterior teeth [J]. Int J Stomatol, 2023, 50(2): 166-171.
[8] Liu Tiqian,Liang Xing,Liu Weiqing,Li Xiaohong,Zhu Rui.. Research progress on the role and mechanism of occlusal trauma in the development of periodontitis [J]. Int J Stomatol, 2023, 50(1): 19-24.
[9] Li Qiong,Yu Weixian. Research progress on resveratrol for the treatment of periodontitis and its bioavailability [J]. Int J Stomatol, 2023, 50(1): 25-31.
[10] Huang Weikun,Xu Qiuyan,Zhou Ting.. Role of baicalin and mechanisms through which baicalin attenuates oxidative stress injury induced by lipopolysaccharide on macrophages [J]. Int J Stomatol, 2022, 49(5): 521-528.
[11] Zhou Jianpeng,Xie Xudong,Zhao Lei,Wang Jun.. Research progress on the roles and mechanisms of T-helper 17 cells and interleukin-17 in periodontitis [J]. Int J Stomatol, 2022, 49(5): 586-592.
[12] Chen Huiyu,Bai Mingru,Ye Ling.. Progress in understanding the correlations between semaphorin 3A and common oral diseases [J]. Int J Stomatol, 2022, 49(5): 593-599.
[13] Zhou Jiajia,Zhao Lei,Xu Xin. Research progress on the genetic polymorphism of periodontitis [J]. Int J Stomatol, 2022, 49(4): 432-440.
[14] Zhu Jiani,Su Qin. Research status of the use of root canal and periapical microflora in refractory periapical periodontitis [J]. Int J Stomatol, 2022, 49(3): 283-289.
[15] Ma Yu,Zuo Yu,Zhang Xin. Photodynamic therapy as an adjunct to periodontitis: a meta-analysis [J]. Int J Stomatol, 2022, 49(3): 305-316.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .