Int J Stomatol ›› 2019, Vol. 46 ›› Issue (5): 593-603.doi: 10.7518/gjkq.2019056

• Reviews • Previous Articles     Next Articles

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 E-mail:lililiuyi@163.com
  • Supported by:
    This study was supported by Capital Medical Development Research Fund Project(2016-2-2141)

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

CLC Number: 

  • R781.4

TrendMD: 

Fig 1

DNA methylation mechanism"

Fig 2

The effects of DNA methylation on TLRs-mediated intracellular signaling pathways"

[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] Fu Yu, He Wei, Huang Lan. Ferroptosis and its implication in oral diseases [J]. Int J Stomatol, 2024, 51(1): 36-44.
[2] Luo Xiaojie,Wang Dexu,Chen Xiaotao. Relationship between periodontitis and ferroptosis based on bioinformatics analysis [J]. Int J Stomatol, 2023, 50(6): 661-668.
[3] 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.
[4] 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.
[5] 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.
[6] Xu Zhibo,Meng Xiuping.. Research progress on mechanism of Enterococcus faecalis escaping host immune defense [J]. Int J Stomatol, 2023, 50(5): 613-617.
[7] 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.
[8] 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.
[9] 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.
[10] 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.
[11] Cheng Yifan,Qin Xu,Jiang Ming,Zhu Guang-xun.. Research progress on innate lymphoid cells in periodontal diseases [J]. Int J Stomatol, 2023, 50(1): 32-36.
[12] 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.
[13] 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.
[14] 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.
[15] Zhou Jiajia,Zhao Lei,Xu Xin. Research progress on the genetic polymorphism of periodontitis [J]. Int J Stomatol, 2022, 49(4): 432-440.
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(05): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .