国际口腔医学杂志

国际口腔医学杂志 ›› 2019, Vol. 46 ›› Issue (5): 593-603.doi: 10.7518/gjkq.2019056

• 综述 • 上一篇    下一篇

甲基化对牙周炎发生与发展的影响及临床应用

姜亦洋,刘怡()   

  1. 首都医科大学附属北京口腔医院牙周科,全牙再生与口腔组织功能重建北京市重点实验室,组织再生免疫学实验室 北京 100050
  • 收稿日期:2018-09-20 修回日期:2019-04-05 出版日期:2019-09-01 发布日期:2019-09-10
  • 通讯作者: 刘怡
  • 作者简介:姜亦洋,硕士,Email： 15901135199@163.com
  • 基金资助:
    首都卫生发展科研专项项目(2016-2-2141)

Effects of methylation on the occurrence and development of periodontitis and its clinical application

Jiang Yiyang,Liu Yi()   

  1. Laboratory of Tissue Regeneration and Immunology and Dept. of Periodontics, Beijing Key Laboratory for Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing 100050, China
  • Received:2018-09-20 Revised:2019-04-05 Online:2019-09-01 Published:2019-09-10
  • Contact: Yi Liu
  • Supported by:
    This study was supported by Capital Medical Development Research Fund Project(2016-2-2141)

RichHTML

19

PDF (PC)

555

摘要：

牙周炎主要是由局部因素引起的牙周支持组织的慢性炎症,细菌感染与宿主免疫反应之间的抗衡影响着疾病的发生、发展。甲基化作为表观遗传修饰的一种,在这其中起到了举足轻重的作用,也成为近年来的热点,它可通过改变染色质的结构选择性地激活或抑制某些基因,影响炎症过程中炎性因子、信号分子、细胞外基质分子的表达,进而调控宿主的免疫水平。对甲基化模式的研究不仅可以增加人们对牙周炎的认识,也对临床有着深远的意义,有助于人们探索治疗牙周炎的新途径,改善牙周炎的预后和转归,是未来重要的研究内容。本文从甲基化修饰的角度对牙周炎相关的研究进展作一综述。

关键词: 甲基化, 牙周炎, 细胞因子

Abstract:

Periodontitis is a chronic inflammation of the supporting periodontal tissues caused by local factors. The counterbalance between bacterial infection and host immune response influences the occurrence and development of this disease. As a kind of epigenetic modification, methylation plays a critical role in this process and has become a research hotspot in recent years. Methylation can activate or inhibit certain genes by altering the structure of chromatin, thereby affecting the expression of inflammatory factors, signaling molecules, and extracellular matrix molecules during inflammation. Thus, methylation can regulate host immunity. Studying methylation patterns can contribute to the public understanding of periodontitis and have profound clinical significance. New ways to treat periodontitis and improve its prognosis need to be explored. This article reviews the research progress of periodontitis from the perspective of methylation modification.

Key words: methylation, periodontitis, cytokine

中图分类号: 

  • R781.4

图 1

DNA甲基化机制 DNA甲基化普遍发生在DNA链中的CpG二核苷酸上,这些CpG岛主要位于基因的启动子区域。当调控区发生甲基化时,由甲基转移酶介导,CpG位点上发生特定序列的甲基化,导致DNA结构浓缩,从而干扰转录因子进入启动子区域,使基因沉默、抑制转录。而当调控区未发生甲基化时,启动子区域的DNA能暴露出与转录因子相结合的位点,使转录正常进行、基因表达正常。"

图 2

DNA甲基化影响TLR介导的细胞内信号通路 牙周炎病原微生物表面存在大量的LPS,当细菌入侵机体时,LPS被巨噬细胞、树突状细胞、牙龈上皮细胞表面的TLR-2和TLR-4识别,激活宿主免疫应答。其中在TLR受体激活的信号通路中,DNA甲基化起了关键调控作用。在牙周炎患者中,TLR基因中的CpG位点存在不同的DNA甲基化,这些位点位于启动子区域NF-κB结合位点的周围,DNA甲基化的改变可以影响NF-κB与启动子的结合,从而影响TLR的表达,并会进一步影响宿主产生促炎性细胞因子,如IL-1、IL-6、IL-8和TNF-α,调节和改变宿主免疫,从而影响牙周炎的进展。"

[1] Hajishengallis G . Periodontitis: from microbial immune subversion to systemic inflammation[J]. Nat Rev Immunol, 2015,15(1):30-44.
[2] Genco RJ, Borgnakke WS . Risk factors for periodontal disease[J]. Periodontol 2000, 2013,62(1):59-94.
[3] Laine ML, Crielaard W, Loos BG . Genetic susceptibility to periodontitis[J]. Periodontol 2000, 2012,58(1):37-68.
[4] De Souza AP, Planello AC, Marques MR , et al. High- throughput DNA analysis shows the importance of methylation in the control of immune inflammatory gene transcription in chronic periodontitis[J]. Clin Epigenetics, 2014,6(1):15.
[5] Sadakierska-Chudy A, Kostrzewa RM, Filip M . A comprehensive view of the epigenetic landscape part Ⅰ: DNA methylation, passive and active DNA demethylation pathways and histone variants[J]. Neurotox Res, 2015,27(1):84-97.
[6] Ngollo M, Dagdemir A, Karsli-Ceppioglu S , et al. Epigenetic modifications in prostate cancer[J]. Epigenomics, 2014,6(4):415-426.
[7] Lindroth AM, Park YJ . Epigenetic biomarkers: a step forward for understanding periodontitis[J]. J Periodontal Implant Sci, 2013,43(3):111-120.
[8] Seo JY, Park YJ, Yi YA , et al. Epigenetics: general characteristics and implications for oral health[J]. Restor Dent Endod, 2015,40(1):14-22.
[9] Jones PA, Liang G . Rethinking how DNA methylation patterns are maintained[J]. Nat Rev Genet, 2009,10(11):805-811.
[10] Deng G, Chen A, Pong E , et al. Methylation in hMLH1 promoter interferes with its binding to transcription factor CBF and inhibits gene expression[J]. Oncogene, 2001,20(48):7120-7127.
[11] Egger G, Liang G, Aparicio A , et al. Epigenetics in human disease and prospects for epigenetic therapy[J]. Nature, 2004,429(6990):457-463.
[12] Bayarsaihan D . Epigenetic mechanisms in inflammation[J]. J Dent Res, 2011,90(1):9-17.
[13] Lod S, Johansson T, Abrahamsson KH , et al. The influence of epigenetics in relation to oral health[J]. Int J Dent Hyg, 2014,12(1):48-54.
[14] Barros SP, Offenbacher S . Modifiable risk factors in periodontal disease: epigenetic regulation of gene expression in the inflammatory response[J]. Periodontol 2000, 2014,64(1):95-110.
[15] Larsson L, Castilho RM, Giannobile WV . Epigenetics and its role in periodontal diseases: a state-of-the-art review[J]. J Periodontol, 2015,86(4):556-568.
[16] Luo Y, Peng X, Duan D , et al. Epigenetic regulations in the pathogenesis of periodontitis[J]. Curr Stem Cell Res Ther, 2018,13(2):144-150.
[17] Lee DY, Teyssier C, Strahl BD , et al. Role of protein methylation in regulation of transcription[J]. Endocr Rev, 2005,26(2):147-170.
[18] Tachibana M, Ueda J, Fukuda M , et al. Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9[J]. Genes Dev, 2005,19(7):815-826.
[19] Gary JD, Clarke S . RNA and protein interactions modulated by protein arginine methylation[J]. Prog Nucleic Acid Res Mol Biol, 1998,61:65-131.
[20] Wilson AG . Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases[J]. J Periodontol, 2008,79(8 Suppl):1514-1519.
[21] Costa PP, Trevisan GL, Macedo GO , et al. Salivary interleukin-6, matrix metalloproteinase-8, and osteoprotegerin in patients with periodontitis and diabetes[J]. J Periodontol, 2010,81(3):384-391.
[22] Nile CJ, Read RC, Akil M , et al. Methylation status of a single CpG site in the IL6 promoter is related to IL6 messenger RNA levels and rheumatoid arthritis[J]. Arthritis Rheum, 2008,58(9):2686-2693.
[23] Ishida K, Kobayashi T, Ito S , et al. Interleukin-6 gene promoter methylation in rheumatoid arthritis and chronic periodontitis[J]. J Periodontol, 2012,83(7):917-925.
[24] Kobayashi T, Ishida K, Yoshie H . Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis[J]. Arch Oral Biol, 2016,69:89-94.
[25] Remick DG . Interleukin-8[J]. Crit Care Med, 2005,33(12 Suppl):S466-S467.
[26] Scapini P, Lapinet-Vera JA, Gasperini S , et al. The neutrophil as a cellular source of chemokines[J]. Immunol Rev, 2000,177:195-203.
[27] Marshall JC . Neutrophils in the pathogenesis of sepsis[J]. Crit Care Med, 2005,33(12 Suppl):S502-S505.
[28] Oliveira NF, Damm GR, Andia DC , et al. DNA methylation status of the IL8 gene promoter in oral cells of smokers and non-smokers with chronic periodontitis[J]. J Clin Periodontol, 2009,36(9):719-725.
[29] Andia DC, de Oliveira NF, Casarin RC , et al. DNA methylation status of the IL8 gene promoter in aggressive periodontitis[J]. J Periodontol, 2010,81(9):1336-1341.
[30] Szalmás A, Bánáti F, Koroknai A , et al. Lineage-specific silencing of human IL-10 gene expression by promoter methylation in cervical cancer cells[J]. Eur J Cancer, 2008,44(7):1030-1038.
[31] Lappin DF , MacLeod CP, Kerr A, et al. Anti-inflammatory cytokine IL-10 and T cell cytokine profile in periodontitis granulation tissue[J]. Clin Exp Immunol, 2001,123(2):294-300.
[32] Viana MB, Cardoso FP, Diniz MG , et al. Methylation pattern of IFN-γ and IL-10 genes in periodontal tissues[J]. Immunobiology, 2011,216(8):936-941.
[33] Garlet GP, Martins W Jr, Ferreira BR , et al. Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease[J]. J Periodontal Res, 2003,38(2):210-217.
[34] Zhang S, Crivello A, Offenbacher S , et al. Interferon-gamma promoter hypomethylation and increased expression in chronic periodontitis[J]. J Clin Periodontol, 2010,37(11):953-961.
[35] Dutzan N, Vernal R, Hernandez M , et al. Levels of interferon-gamma and transcription factor T-bet in progressive periodontal lesions in patients with chronic periodontitis[J]. J Periodontol, 2009,80(2):290-296.
[36] Ekhlassi S, Scruggs LY, Garza T , et al. Porphyromonas gingivalis lipopolysaccharide induces tumor necrosis factor-alpha and interleukin-6 secretion, and CCL25 gene expression, in mouse primary gingival cell lines: interleukin-6-driven activation of CCL2[J]. J Periodontal Res, 2008,43(4):431-439.
[37] Aggarwal S, Gurney AL . IL-17: prototype member of an emerging cytokine family[J]. J Leukoc Biol, 2002,71(1):1-8.
[38] Mitani A, Niedbala W, Fujimura T , et al. Increased expression of interleukin (IL)-35 and IL-17, but not IL-27, in gingival tissues with chronic periodontitis[J]. J Periodontol, 2015,86(2):301-309.
[39] Shaker OG, Ghallab NA . IL-17 and IL-11 GCF levels in aggressive and chronic periodontitis patients: relation to PCR bacterial detection[J]. Mediators Inflamm, 2012,2012:174764.
[40] Costa MF, Bornstein VU, Candéa AL , et al. CCL25 induces α4β7 integrin-dependent migration of IL-17 + γδ T lymphocytes during an allergic reaction [J]. Eur J Immunol, 2012,42(5):1250-1260.
[41] Schulz S, Immel UD, Just L , et al. Epigenetic characteristics in inflammatory candidate genes in aggressive periodontitis[J]. Hum Immunol, 2016,77(1):71-75.
[42] Graves DT, Cochran D . The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction[J]. J Periodontol, 2003,74(3):391-401.
[43] Shapira L, Takashiba S, Champagne C , et al. Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes[J]. J Immunol, 1994,153(4):1818-1824.
[44] Tervahartiala T, Koski H, Xu JW , et al. Tumor necrosis factor-alpha and its receptors, p55 and p75, in gingiva of adult periodontitis[J]. J Dent Res, 2001,80(6):1535-1539.
[45] Górska R, Gregorek H, Kowalski J , et al. Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis[J]. J Clin Periodontol, 2003,30(12):1046-1052.
[46] Kurtiş B, Tüter G, Serdar M , et al. Gingival crevicular fluid levels of monocyte chemoattractant protein- 1 and tumor necrosis factor-alpha in patients with chronic and aggressive periodontitis[J]. J Periodontol, 2005,76(11):1849-1855.
[47] Zhang S, Barros SP, Moretti AJ , et al. Epigenetic regulation of TNFA expression in periodontal disease[J]. J Periodontol, 2013,84(11):1606-1616.
[48] Kojima A, Kobayashi T, Ito S , et al. Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis[J]. J Periodontal Res, 2016,51(3):350-358.
[49] Smith WL , DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology[J]. Annu Rev Biochem, 2000,69:145-182.
[50] Noguchi K, Yanai M, Shitashige M , et al. Cyclooxygenase-2-dependent prostaglandin production by peripheral blood monocytes stimulated with lipopolysaccharides isolated from periodontopathogenic bacteria[J]. J Periodontol, 2000,71(10):1575-1582.
[51] Noguchi K, Ishikawa I . The roles of cyclooxygenase- 2 and prostaglandin E2 in periodontal disease[J]. Periodontol 2000, 2007,43:85-101.
[52] Champagne CM, Buchanan W, Reddy MS , et al. Potential for gingival crevice fluid measures as predictors of risk for periodontal diseases[J]. Periodontol 2000, 2003,31:167-180.
[53] Zhong Y, Slade GD, Beck JD , et al. Gingival crevicular fluid interleukin-1beta, prostaglandin E2 and periodontal status in a community population[J]. J Clin Periodontol, 2007,34(4):285-293.
[54] Zhang S, Barros SP, Niculescu MD , et al. Alteration of PTGS2 promoter methylation in chronic periodontitis[J]. J Dent Res, 2010,89(2):133-137.
[55] Asa’ad F, Bollati V, Pagni G , et al. Evaluation of DNA methylation of inflammatory genes following treatment of chronic periodontitis: a pilot case-control study[J]. J Clin Periodontol, 2017,44(9):905-914.
[56] Ohi T, Uehara Y, Takatsu M , et al. Hypermethylation of CpGs in the promoter of the COL1A1 gene in the aged periodontal ligament[J]. J Dent Res, 2006,85(3):245-250.
[57] Loo WT, Jin L, Cheung MN , et al. Epigenetic change in E-cadherin and COX-2 to predict chronic periodontitis[J]. J Transl Med, 2010,8:110.
[58] Nagarakanti S, Ramya S, Babu P , et al. Differential expression of E-cadherin and cytokeratin 19 and net proliferative rate of gingival keratinocytes in oral epithelium in periodontal health and disease[J]. J Periodontol, 2007,78(11):2197-2202.
[59] Baptista NB, Portinho D, Casarin RC , et al. DNA methylation levels of SOCS1 and LINE-1 in oral epithelial cells from aggressive periodontitis patients[J]. Arch Oral Biol, 2014,59(7):670-678.
[60] Andia DC, Planello AC, Portinho D , et al. DNA methylation analysis of SOCS1, SOCS3, and LINE-1 in microdissected gingival tissue[J]. Clin Oral Investig, 2015,19(9):2337-2344.
[61] Uehara O, Abiko Y, Saitoh M , et al. Lipopolysaccharide extracted from Porphyromonas gingivalis induces DNA hypermethylation of runt-related transcription factor 2 in human periodontal fibroblasts[J]. J Microbiol Immunol Infect, 2014,47(3):176-181.
[62] Akira S, Takeda K, Kaisho T . Toll-like receptors: critical proteins linking innate and acquired immunity[J]. Nat Immunol, 2001,2(8):675-680.
[63] Kumar H, Kawai T, Akira S . Toll-like receptors and innate immunity[J]. Biochem Biophys Res Commun, 2009,388(4):621-625.
[64] Kocgozlu L, Elkaim R, Tenenbaum H , et al. Variable cell responses to P. gingivalis lipopolysaccharide[J]. J Dent Res, 2009,88(8):741-745.
[65] Teng YT . Protective and destructive immunity in the periodontium: part 1—innate and humoral immunity and the periodontium[J]. J Dent Res, 2006,85(3):198-208.
[66] Burns E, Bachrach G, Shapira L , et al. Cutting edge: TLR2 is required for the innate response to Porphyromonas gingivalis: activation leads to bacterial persistence and TLR2 deficiency attenuates induced alveolar bone resorption[J]. J Immunol, 2006,177(12):8296-8300.
[67] Medzhitov R, Janeway C Jr . Innate immune recognition: mechanisms and pathways[J]. Immunol Rev, 2000,173:89-97.
[68] De Oliveira NF, Andia DC, Planello AC , et al. TLR2 and TLR4 gene promoter methylation status during chronic periodontitis[J]. J Clin Periodontol, 2011,38(11):975-983.
[69] de Faria Amormino SA, Arão TC, Saraiva AM , et al. Hypermethylation and low transcription of TLR2 gene in chronic periodontitis[J]. Hum Immunol, 2013,74(9):1231-1236.
[70] Johnson CM, Tapping RI . Microbial products stimulate human Toll-like receptor 2 expression through histone modification surrounding a proximal NF-kappaB-binding site[J]. J Biol Chem, 2007,282(43):31197-31205.
[71] Mize TW, Sundararaj KP, Leite RS , et al. Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis[J]. J Periodontal Res, 2015,50(3):315-319.
[72] Zhang T, Wu J, Ungvijanpunya N , et al. Smad6 methylation represses NFκB activation and periodontal inflammation[J]. J Dent Res, 2018,97(7):810-819.
[73] Abiko Y, Uehara O, Fukumoto S , et al. Epigenetics of oral infection and inflammatory diseases—DNA methylation changes in infections and inflammation diseases[J]. J Oral Biosci, 2014,56(4):105-109.
[74] Takai R, Uehara O, Harada F , et al. DNA hypermethylation of extracellular matrix-related genes in human periodontal fibroblasts induced by stimulation for a prolonged period with lipopolysaccharide derived from Porphyromonas gingivalis[J]. J Periodontal Res, 2016,51(4):508-517.
[75] Li W, Zhu Y, Singh P , et al. Association of common variants in MMPs with periodontitis risk[J]. Dis Markers, 2016,2016:1545974.
[76] He CY, Gao XQ, Jiang LP . The impact of smoking on levels of chronic periodontitis-associated biomarkers[J]. Exp Mol Pathol, 2016,101(1):110-115.
[77] Li X, Lu J, Teng W , et al. Quantitative evaluation of MMP-9 and TIMP-1 promoter methylation in chronic periodontitis[J]. DNA Cell Biol, 2018,37(3):168-173.
[78] Kubota M, Tanno-Nakanishi M, Yamada S , et al. Effect of smoking on subgingival microflora of patients with periodontitis in Japan[J]. BMC Oral Health, 2011,11:1.
[79] Zini A, Sgan-Cohen HD, Marcenes W . Socio-economic position, smoking, and plaque: a pathway to severe chronic periodontitis[J]. J Clin Periodontol, 2011,38(3):229-235.
[80] Fiorini T, Musskopf ML, Oppermann RV , et al. Is there a positive effect of smoking cessation on periodontal health? A systematic review[J]. J Periodontol, 2014,85(1):83-91.
[81] Khan S . Effect of smoking on periodontal health[J]. Dis Mon, 2011,57(4):214-217.
[82] Cho YD, Kim PJ, Kim HG , et al. Transcriptomics and methylomics in chronic periodontitis with tobacco use: a pilot study[J]. Clin Epigenetics, 2017,9:81.
[83] Tomi N, Fukuyo Y, Arakawa S , et al. Pro-inflammatory cytokine production from normal human fibroblasts is induced by Tannerella forsythia detaching factor[J]. J Periodontal Res, 2008,43(2):136-142.
[84] Uehara A, Naito M, Imamura T , et al. Dual regulation of interleukin-8 production in human oral epithelial cells upon stimulation with gingipains from Porphyromonas gingivalis[J]. J Med Microbiol, 2008,57(Pt 4):500-507.
[85] Wu H, Lippmann JE, Oza JP , et al. Inactivation of DNA adenine methyltransferase alters virulence factors in Actinobacillus actinomycetemcomitans[J]. Oral Microbiol Immunol, 2006,21(4):238-244.
[86] Christman JK . 5-Azacytidine and 5-aza-2’-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy[J]. Oncogene, 2002,21(35):5483-5495.
[87] Sufaru IG, Beikircher G, Weinhaeusel A , et al. Inhibitors of DNA methylation support TGF-β1-induced IL11 expression in gingival fibroblasts[J]. J Periodontal Implant Sci, 2017,47(2):66-76.
[88] Larsson L . Current concepts of epigenetics and its role in periodontitis[J]. Curr Oral Health Rep, 2017,4(4):286-293.
[89] Cho Y, Kim B, Bae H , et al. Direct gingival fibroblast/ osteoblast transdifferentiation via epigenetics[J]. J Dent Res, 2017,96(5):555-561.
[90] Rabineau M, Flick F, Mathieu E , et al. Cell guidance into quiescent state through chromatin remodeling induced by elastic modulus of substrate[J]. Biomaterials, 2015,37:144-155.
[91] Lv L, Liu Y, Zhang P , et al. The nanoscale geometry of TiO2 nanotubes influences the osteogenic differentiation of human adipose-derived stem cells by modulating H3K4 trimethylation[J]. Biomaterials, 2015,39:193-205.
[92] Nguyen DV, Li Calzi S, Shaw LC , et al. An ocular view of the IGF-IGFBP system[J]. Growth Horm IGF Res, 2013,23(3):45-52.
[93] Wang S, Mu J, Fan Z , et al. Insulin-like growth factor 1 can promote the osteogenic differentiation and osteogenesis of stem cells from apical papilla[J]. Stem Cell Res, 2012,8(3):346-356.
[94] Yu S, Long J, Yu J , et al. Analysis of differentiation potentials and gene expression profiles of mesenchymal stem cells derived from periodontal ligament and Wharton’s jelly of the umbilical cord[J]. Cells Tissues Organs, 2013,197(3):209-223.
[95] Liu D, Wang Y, Jia Z , et al. Demethylation of IGFBP5 by histone demethylase KDM6B promotes mesenchymal stem cell-mediated periodontal tissue regeneration by enhancing osteogenic differentiation and anti-inflammation potentials[J]. Stem Cells, 2015,33(8):2523-2536.
[96] Grover V, Kapoor A, Malhotra R , et al. Epigenetics and periodontal disease: hope to tame the untameable[J]. Curr Gene Ther, 2014,14(6):473-481.
[1] 傅豫, 何薇, 黄兰. 铁死亡在口腔疾病中的研究进展[J]. 国际口腔医学杂志, 2024, 51(1): 36-44.
[2] 罗晓洁,王德续,陈晓涛. 基于生物信息学分析铁死亡调控基因与牙周炎的关系[J]. 国际口腔医学杂志, 2023, 50(6): 661-668.
[3] 黄元鸿,彭显,周学东. 骨碎补在治疗口腔骨相关疾病的研究进展[J]. 国际口腔医学杂志, 2023, 50(6): 679-685.
[4] 龚美灵,程兴群,吴红崑. 牙周炎与帕金森病相关性的研究进展[J]. 国际口腔医学杂志, 2023, 50(5): 587-593.
[5] 孙佳,韩烨,侯建霞. 白细胞介素-6-铁调素信号轴调控牙周炎相关性贫血致病机制的研究进展[J]. 国际口腔医学杂志, 2023, 50(3): 329-334.
[6] 刘体倩,梁星,刘蔚晴,李晓虹,朱睿. 咬合创伤在牙周炎发生发展中的作用及机制的研究进展[J]. 国际口腔医学杂志, 2023, 50(1): 19-24.
[7] 李琼,于维先. 白藜芦醇治疗牙周炎及其生物利用度的研究进展[J]. 国际口腔医学杂志, 2023, 50(1): 25-31.
[8] 成益凡,秦旭,姜鸣,朱光勋. 牙周病中固有淋巴细胞的研究进展[J]. 国际口腔医学杂志, 2023, 50(1): 32-36.
[9] 黄伟琨,徐秋艳,周婷. 黄芩苷抑制脂多糖促巨噬细胞氧化应激损伤作用的研究[J]. 国际口腔医学杂志, 2022, 49(5): 521-528.
[10] 周剑鹏,谢旭东,赵蕾,王骏. 辅助性T细胞17及白细胞介素17在牙周炎中的作用及机制的研究进展[J]. 国际口腔医学杂志, 2022, 49(5): 586-592.
[11] 陈荟宇,白明茹,叶玲. 信号素3A与口腔常见病关系的研究进展[J]. 国际口腔医学杂志, 2022, 49(5): 593-599.
[12] 周佳佳,赵蕾,徐欣. 牙周炎相关基因多态性的研究进展[J]. 国际口腔医学杂志, 2022, 49(4): 432-440.
[13] 马玉,左玉,张鑫. 光动力疗法辅助治疗牙周炎治疗效果的Meta分析[J]. 国际口腔医学杂志, 2022, 49(3): 305-316.
[14] 钱素婷,丁玲敏,纪雅宁,林军. 微小RNA在牙周炎龈沟液中的表达差异及对牙周炎的调控机制[J]. 国际口腔医学杂志, 2022, 49(3): 349-355.
[15] 蒋端,申道南,赵蕾,吴亚菲. 内皮发育调节基因-1与牙周炎相关性的研究进展[J]. 国际口腔医学杂志, 2022, 49(2): 244-248.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 王昆润. 修补颌骨缺损的新型生物学相容材料[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 陆加梅. 不可复性关节盘移位患者术前张口度与关节镜术后疗效的相关性[J]. 国际口腔医学杂志, 1999, 26(06): .
[3] 王昆润. 咀嚼口香糖对牙周组织微循环的影响[J]. 国际口腔医学杂志, 1999, 26(06): .
[4] 宋红. 青少年牙周炎外周血分叶核粒细胞的趋化功能[J]. 国际口腔医学杂志, 1999, 26(06): .
[5] 高卫民,李幸红. 发达国家牙医学院口腔种植学教学现状[J]. 国际口腔医学杂志, 1999, 26(06): .
[6] 侯锐. 正畸患者釉白斑损害的纵向激光荧光研究[J]. 国际口腔医学杂志, 1999, 26(05): .
[7] 轩东英. 不同赋形剂对氢氧化钙抗菌效果的影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[8] 房兵. 唇腭裂新生儿前颌骨矫正方法及对上颌骨生长发育的影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[9] 杨美祥. 前牙厚度在预测上下颌牙量协调性中的作用[J]. 国际口腔医学杂志, 1999, 26(04): .
[10] 赵艳丽. 手术刀、电凝、CO_2和KTP激光对大鼠舌部创口的作用[J]. 国际口腔医学杂志, 1999, 26(04): .