Skip to content
2000
Volume 32, Issue 14
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Periodontitis is a complex polymicrobial disease of the oral cavity that affects tooth-supporting tissues. It is caused by multiple factors, such as pathogenic bacteria, genetic predisposition, and host immune response factors. The pathogenesis of periodontal disease involves the complex interrelations among bacterial toxins, several populations of cells, and host cell-secreted inflammatory mediators. Generally, periodontitis is characterized by the formation of intricate and varied biofilms of microbes on the tooth surface, commonly known as dental plaque. Activation of defense cells is characterized by releasing inflammatory mediators, such as proteases, acidic metabolites, cytokines, interleukins, and chemokines, which destroy tissue and ultimately cause bone resorption. The individual periodontal condition has a significant impact on systemic homeostasis, and its disruption can cause the development of some metabolic disorders. This review article summarizes the latest studies on the pathogenesis of periodontitis and describes the role of inflammatory mediators and genetic polymorphism in individuals, as well as relationships with some metabolic conditions. The information is collected from PubMed, Scopus, ScienceDirect, SpringerLink, and clinicaltrials.gov.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673302701240509103537
2024-05-16
2025-10-08

  • From This Site

    /content/journals/cmc/10.2174/0109298673302701240509103537
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. RayR.R. Periodontitis: An oral disease with severe consequences.Appl. Biochem. Biotechnol.20231951173210.1007/s12010‑022‑04127‑936098930
     [Google Scholar]
  2. YangB. PangX. LiZ. ChenZ. WangY. Immunomodulation in the treatment of periodontitis: Progress and perspectives.Front. Immunol.20211278137810.3389/fimmu.2021.78137834868054
     [Google Scholar]
  3. NazirM. Al-AnsariA. Al-KhalifaK. AlharekyM. GaffarB. AlmasK. Global prevalence of periodontal disease and lack of its surveillance.ScientificWorldJournal202020201810.1155/2020/214616032549797
     [Google Scholar]
  4. KowalskiJ. NowakM. GórskiB. GórskaR. What has immunology brought to periodontal disease in recent years?Arch. Immunol. Ther. Exp.20227012610.1007/s00005‑022‑00662‑936245042
     [Google Scholar]
  5. HutorN.S. PidruchnaS.R. MelnykN.A. AvdeevO.V. BoykivA.B. KovtunN.Y. SkochyloO.V. TverdokhlibN.O. Goncharuk-KhomynM.Y. The role of prooxidant-antioxidant system in the development of alveolitis after teeth extraction.JIDMR2020132561565
     [Google Scholar]
  6. BenahmedA.G. GasmiA. TippairoteT. MujawdiyaP.K. AvdeevO. ShanaidaY. BjørklundG. Metabolic conditions and peri-implantitis.Antibiotics20221216510.3390/antibiotics1201006536671266
     [Google Scholar]
  7. ClarkD. LevinL. In the dental implant era, why do we still bother saving teeth?J. Endod.20194512S57S6510.1016/j.joen.2019.05.01431623910
     [Google Scholar]
  8. SunY. ShuR. LiC.L. ZhangM.Z. Gram-negative periodontal bacteria induce the activation of Toll-like receptors 2 and 4, and cytokine production in human periodontal ligament cells.J. Periodontol.201081101488149610.1902/jop.2010.10000420528699
     [Google Scholar]
  9. NCT04831060. U.S. National Library of Medicine.2023Available from: https://clinicaltrials.gov./study/NCT04831060?cond=Periodontitis&rank=10&tab=table
  10. NCT05278468. U.S. National Library of Medicine.2023Available from: https://clinicaltrials.gov./study/NCT05278468?cond=Periodontitis&page=4&rank=34
  11. BitencourtF.V. NascimentoG.G. CostaS.A. AndersenA. SandbækA. LeiteF.R.M. Co-occurrence of periodontitis and diabetes-related complications.J. Dent. Res.2023102101088109710.1177/0022034523117989737448314
     [Google Scholar]
  12. Mauri-ObradorsE. MerlosA. Estrugo-DevesaA. Jané-SalasE. López-LópezJ. ViñasM. Benefits of non-surgical periodontal treatment in patients with type 2 diabetes mellitus and chronic periodontitis: A randomized controlled trial.J. Clin. Periodontol.201845334535310.1111/jcpe.1285829265454
     [Google Scholar]
  13. SimpsonT.C. ClarksonJ.E. WorthingtonH.V. MacDonaldL. WeldonJ.C. NeedlemanI. Iheozor-EjioforZ. WildS.H. QureshiA. WalkerA. PatelV.A. BoyersD. TwiggJ. Treatment of periodontitis for glycaemic control in people with diabetes mellitus.Cochrane Database Syst. Rev.202244CD00471435420698
     [Google Scholar]
  14. ZhaoM. XieY. GaoW. LiC. YeQ. LiY. Diabetes mellitus promotes susceptibility to periodontitis-novel insight into the molecular mechanisms.Front. Endocrinol.202314119262510.3389/fendo.2023.119262537664859
     [Google Scholar]
  15. AlbrechtK. de PabloP. EidnerT. HoeseG. WassenbergS. ZinkA. CallhoffJ. Association between RA disease activity and periodontitis defined by tooth loss: Longitudinal and cross-sectional data from two observational studies.Arthritis Care Res.2025772169177
     [Google Scholar]
  16. AvdeevO. DrevnitskaR. BoykivA. VydoinykO. Condition of fagocytosis of experimental animals with periodontitis due to modified reactivity.Med. News201972401404
     [Google Scholar]
  17. MainasG. IdeM. RizzoM. Magan-FernandezA. MesaF. NibaliL. Managing the systemic impact of periodontitis.Medicina202258562110.3390/medicina5805062135630038
     [Google Scholar]
  18. ShcherbaV. KyrylivM. BekusI. KrynytskaI. MarushchakM. KordaM. A comparative study of connective tissue metabolism indices in experimental comorbidity-free periodontitis and periodontitis combined with thyroid dysfunction.J. Med. Life202013221922410.25122/jml‑2019‑011332742517
     [Google Scholar]
  19. BeckJ.D. PapapanouP.N. PhilipsK.H. OffenbacherS. Periodontal medicine: 100 years of progress.J. Dent. Res.201998101053106210.1177/002203451984611331429666
     [Google Scholar]
  20. GrigoriadouM. KoutayasS. MadianosP. StrubJ.-R. Interleukin-1 as a genetic marker for periodontitis.Quintessence Int.201041517525
     [Google Scholar]
  21. Ahmed KhanH.L. MurthykumarK. GanapathyD. Genetic association of the C-C motif chemokine ligand 2 (CCL2) rs1024611 polymorphism with periodontitis.Cureus20231510e4643810.7759/cureus.4643837927745
     [Google Scholar]
  22. BjørklundG. ShanaidaM. LysiukR. ButnariuM. PeanaM. SaracI. StrusO. SmetaninaK. ChirumboloS. Natural compounds and products from an anti-aging perspective.Molecules20222720708410.3390/molecules2720708436296673
     [Google Scholar]
  23. ChenE. WangT. TuY. SunZ. DingY. GuZ. XiaoS. ROS-scavenging biomaterials for periodontitis.J. Mater. Chem. B Mater. Biol. Med.202311348249910.1039/D2TB02319A36468674
     [Google Scholar]
  24. KwonT. LamsterI.B. LevinL. Current concepts in the management of periodontitis.Int. Dent. J.202171646247610.1111/idj.1263034839889
     [Google Scholar]
  25. Gasmi BenahmedA. GasmiA. ArshadM. ShanaidaM. LysiukR. PeanaM. Pshyk-TitkoI. AdamivS. ShanaidaY. BjørklundG. Health benefits of xylitol.Appl. Microbiol. Biotechnol.2020104177225723710.1007/s00253‑020‑10708‑732638045
     [Google Scholar]
  26. Gasmi BenahmedA. GasmiA. DadarM. ArshadM. BjørklundG. The role of sugar-rich diet and salivary proteins in dental plaque formation and oral health.J. Oral Biosci.202163213414110.1016/j.job.2021.01.00733497842
     [Google Scholar]
  27. GasmiB.A. TippairoteT. GasmiA. NoorS. AvdeevO. ShanaidaY. MojganiN. EmadaliA. DadarM. BjørklundG. Periodontitis continuum: Antecedents, triggers, mediators, and treatment strategies.Curr. Med. Chem.2024416775680010.2174/0109298673265862231020051338
     [Google Scholar]
  28. EbersoleJ. LambertJ. BushH. HujaP. BasuA. Serum nutrient levels and aging effects on periodontitis.Nutrients20181012198610.3390/nu1012198630558282
     [Google Scholar]
  29. LiW. ShangQ. YangD. PengJ. ZhaoH. XuH. ChenQ. Abnormal micronutrient intake is associated with the risk of periodontitis: A dose-response association study based on NHANES 2009–2014.Nutrients20221412246610.3390/nu1412246635745196
     [Google Scholar]
  30. UstianowskiŁ. UstianowskaK. GurazdaK. RusińskiM. OstrowskiP. PawlikA. The role of vitamin C and vitamin D in the pathogenesis and therapy of periodontitis- narrative review.Int. J. Mol. Sci.2023247677410.3390/ijms2407677437047746
     [Google Scholar]
  31. GasmiA. ShanaidaM. OleshchukO. SemenovaY. MujawdiyaP.K. IvankivY. PokryshkoO. NoorS. PiscopoS. AdamivS. BjørklundG. Natural ingredients to improve immunity.Pharmaceuticals202316452810.3390/ph1604052837111285
     [Google Scholar]
  32. IovaG.M. CalniceanuH. PopaA. SzuhanekC.A. MarcuO. CiavoiG. ScrobotaI. The antioxidant effect of curcumin and rutin on oxidative stress biomarkers in experimentally induced periodontitis in hyperglycemic wistar rats.Molecules2021265133210.3390/molecules2605133233801378
     [Google Scholar]
  33. NewmanH. WilsonM. Dental plaque revisited: Oral biofilms in health and diseases.Cardiff, United KingdomBioline1999
     [Google Scholar]
  34. FongS.B. BoyerE. Bonnaure-MalletM. MeuricV. Microbiota in periodontitis: Advances in the omic era.Adv. Exp. Med. Biol.20221373194310.1007/978‑3‑030‑96881‑6_235612791
     [Google Scholar]
  35. CarranzaF.A. NewmanM. TakeiH. KlokkevoldP.R. Carranza’s Clynical PeriodontologySaunders Elsevier2006121286
     [Google Scholar]
  36. HutterG. SchlagenhaufU. ValenzaG. HornM. BurgemeisterS. ClausH. VogelU. Molecular analysis of bacteria in periodontitis: Evaluation of clone libraries, novel phylotypes and putative pathogens.Microbiology20031491677510.1099/mic.0.25791‑012576581
     [Google Scholar]
  37. HoltS.C. EbersoleJ.L. Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the ‘red complex’, a prototype polybacterial pathogenic consortium in periodontitis.Periodontol. 200020053817212210.1111/j.1600‑0757.2005.00113.x15853938
     [Google Scholar]
  38. ZhangZ. LiuD. LiuS. ZhangS. PanY. The role of Porphyromonas gingivalis outer membrane vesicles in periodontal disease and related systemic diseases.Front. Cell. Infect. Microbiol.20211058591710.3389/fcimb.2020.58591733585266
     [Google Scholar]
  39. HbibiA. BouzianeA. LyoussiB. ZouhdiM. BenazzaD. Aggregatibacter actinomycetemcomitans: From basic to advanced research.Adv. Exp. Med. Biol.20221373456710.1007/978‑3‑030‑96881‑6_335612792
     [Google Scholar]
  40. DamgaardC. DanielsenA.K. EnevoldC. ReinholdtJ. HolmstrupP. NielsenC.H. MassarentiL. Circulating antibodies against leukotoxin A as marker of periodontitis Grades B and C and oral infection with Aggregatibacter actinomycetemcomitans.J. Periodontol.202192121795180410.1002/JPER.20‑089533749825
     [Google Scholar]
  41. MoylanA.D. PatelD.T. O’BrienC. SchulerE.J.A. HinsonA.N. MarconiR.T. MillerD.P. Characterization of c-di-AMP signaling in the periodontal pathobiont, Treponema denticola.Mol. Oral Microbiol.2024omi.1245810.1111/omi.1245838436552
     [Google Scholar]
  42. AS. GirijaA.S.S. PriyadharsiniV.J. Molecular characterization of the glyA gene from the clinical isolates of Tannerella forsythia.Cureus2024162e5490910.7759/cureus.5490938544640
     [Google Scholar]
  43. BartoldP.M. Van DykeT.E. An appraisal of the role of specific bacteria in the initial pathogenesis of periodontitis.J. Clin. Periodontol.201946161110.1111/jcpe.1304630556922
     [Google Scholar]
  44. NibaliL. The periodontal diseases: Microbial diseases or diseases of the host response?The Human Microbiota and Chronic Disease: Dysbiosis as a Cause of Human Pathology2016217
     [Google Scholar]
  45. José RicardoK. Yumi Umeda SuzukiT. Fumico Umeda KinaE. KinaJ. KinaM. José Ricardo Kina Non-inflammatory destructive periodontal disease.Open Dent. J.2016101505710.2174/187421060161001005027053968
     [Google Scholar]
  46. PöllänenM.T. SalonenJ.I. UittoV.J. Structure and function of the tooth-pithelial interface in health and disease.Periodontol.2003311123110.1034/j.1600‑0757.2003.03102.x12656993
     [Google Scholar]
  47. SchroederH.E. ListgartenM.A. The gingival tissues: The architecture of periodontal protection.Periodontol. 200019971319112010.1111/j.1600‑0757.1997.tb00097.x9567925
     [Google Scholar]
  48. BosshardtD.D. LangN.P. The junctional epithelium: From health to disease.J. Dent. Res.200584192010.1177/15440591050840010215615869
     [Google Scholar]
  49. CossartP. LecuitM. Interactions of Listeria monocytogenes with mammalian cells during entry and actin-based movement: Bacterial factors, cellular ligands and signaling.EMBO J.199817143797380610.1093/emboj/17.14.37979669997
     [Google Scholar]
  50. KahnR.A. FuH. RoyC.R. Cellular hijacking: A common strategy for microbial infection.Trends Biochem. Sci.200227630831410.1016/S0968‑0004(02)02108‑412069791
     [Google Scholar]
  51. MintyM. CanceilT. SerinoM. BurcelinR. TercéF. Blasco-BaqueV. Oral microbiota-induced periodontitis: A new risk factor of metabolic diseases.Rev. Endocr. Metab. Disord.201920444945910.1007/s11154‑019‑09526‑831741266
     [Google Scholar]
  52. SaidathK. MohantyR. AsopaS.J. JosephM.D. SinghB. RajguruJ.P. SharmaU. Red complex: Polymicrobial conglomerate in oral flora: A review.J. Family Med. Prim. Care20198113480348610.4103/jfmpc.jfmpc_759_1931803640
     [Google Scholar]
  53. YilmazO. WatanabeK. LamontR.J. Involvement of integrins in fimbriae-mediated binding and invasion by Porphyromonas gingivalis.Cell. Microbiol.20024530531410.1046/j.1462‑5822.2002.00192.x12027958
     [Google Scholar]
  54. YilmazÖ. YoungP.A. LamontR.J. KennyG.E. Gingival epithelial cell signalling and cytoskeletal responses to Porphyromonas gingivalis invasion.Microbiology200314992417242610.1099/mic.0.26483‑012949167
     [Google Scholar]
  55. OlsenI. Progulske-FoxA. Invasion of Porphyromonas gingivalis strains into vascular cells and tissue.J. Oral Microbiol.2015712878810.3402/jom.v7.2878826329158
     [Google Scholar]
  56. MartinV. RibeiroI.A.C. AlvesM.M. GonçalvesL. AlmeidaA.J. GrenhoL. FernandesM.H. SantosC.F. GomesP.S. BettencourtA.F. Understanding intracellular trafficking and anti-inflammatory effects of minocycline chitosan-nanoparticles in human gingival fibroblasts for periodontal disease treatment.Int. J. Pharm.201957211882110.1016/j.ijpharm.2019.11882131711981
     [Google Scholar]
  57. PanC. LiuJ. WangH. SongJ. TanL. ZhaoH. PorPhyromonas gingivalis can invade periodontal ligament stem cells.BMC Microbiol.20171713810.1186/s12866‑017‑0950‑528212613
     [Google Scholar]
  58. InabaH. NomuraR. KatoY. TakeuchiH. AmanoA. AsaiF. NakanoK. LamontR.J. Matsumoto-NakanoM. Adhesion and invasion of gingival epithelial cells by Porphyromonas gulae.PLoS One2019143e021330910.1371/journal.pone.021330930870452
     [Google Scholar]
  59. TribbleG.D. LamontR.J. Bacterial invasion of epithelial cells and spreading in periodontal tissue.Periodontol. 20002010521688310.1111/j.1600‑0757.2009.00323.x20017796
     [Google Scholar]
  60. ColomboA.V. Da SilvaC.M. HaffajeeA. ColomboA.P.V. Identification of intracellular oral species within human crevicular epithelial cells from subjects with chronic periodontitis by fluorescence in situ hybridization.J. Periodontal Res.200742323624310.1111/j.1600‑0765.2006.00938.x17451543
     [Google Scholar]
  61. PopovaC. Dosseva-PanovaV. PanovV. Microbiology of periodontal diseases. A review.Biotechnol. Biotechnol. Equip.20132733754375910.5504/BBEQ.2013.0027
     [Google Scholar]
  62. LiJ. ShiJ. PanY. ZhaoY. YanF. LiH. LeiL. Transcription modulation by CDK9 regulates inflammatory genes and RIPK3-MLKL-mediated necroptosis in periodontitis progression.Sci. Rep.2019911736910.1038/s41598‑019‑53910‑y31758083
     [Google Scholar]
  63. ShaoH. DemuthD.R. Quorum sensing regulation of biofilm growth and gene expression by oral bacteria and periodontal pathogens.Periodontol. 20002010521536710.1111/j.1600‑0757.2009.00318.x20017795
     [Google Scholar]
  64. NakayamaM. InoueT. NaitoM. NakayamaK. OharaN. Attenuation of the phosphatidylinositol 3-kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp.J. Biol. Chem.201529085190520210.1074/jbc.M114.59161025564612
     [Google Scholar]
  65. SongG. OuyangG. BaoS. The activation of Akt/PKB signaling pathway and cell survival.J. Cell. Mol. Med.200591597110.1111/j.1582‑4934.2005.tb00337.x15784165
     [Google Scholar]
  66. EngelmanJ.A. LuoJ. CantleyL.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism.Nat. Rev. Genet.20067860661910.1038/nrg187916847462
     [Google Scholar]
  67. SotoC. BugueñoI. HoareA. GonzalezS. VenegasD. SalinasD. Melgar-RodríguezS. VernalR. GamonalJ. QuestA.F.G. Pérez-DonosoJ.M. BravoD. The Porphyromonas gingivalis O antigen is required for inhibition of apoptosis in gingival epithelial cells following bacterial infection.J. Periodontal Res.201651451852810.1111/jre.1233126530544
     [Google Scholar]
  68. OkinagaT. KasaiH. TsujisawaT. NishiharaT. Role of caspases in cleavage of lamin A/C and PARP during apoptosis in macrophages infected with a periodontopathic bacterium.J. Med. Microbiol.200756101399140410.1099/jmm.0.47193‑017893180
     [Google Scholar]
  69. KasaiH. YamamotoK. KosekiT. YokotaM. NishiharaT. Involvement of caspase activation through release of cytochrome c from mitochondria in apoptotic cell death of macrophages infected with Actinobacillus actinomycetemcomitans.FEMS Microbiol. Lett.20042331293510.1016/j.femsle.2004.01.03415043866
     [Google Scholar]
  70. SongB. ZhangY.L. ChenL.J. ZhouT. HuangW.K. ZhouX. ShaoL.Q. The role of Toll-like receptors in periodontitis.Oral Dis.201723216818010.1111/odi.1246826923115
     [Google Scholar]
  71. ChenY.C. LiuC.M. JengJ.H. KuC.C. Association of pocket epithelial cell proliferation in periodontitis with TLR9 expression and inflammatory response.J. Formos. Med. Assoc.2014113854955610.1016/j.jfma.2012.07.04325037760
     [Google Scholar]
  72. SwaminathanV. PrakasamS. PuriV. SrinivasanM. Role of salivary epithelial toll-like receptors 2 and 4 in modulating innate immune responses in chronic periodontitis.J. Periodontal Res.201348675776510.1111/jre.1206623679005
     [Google Scholar]
  73. HuangQ. DongX. Prevalence of periodontal disease in middle-aged and elderly patients and its influencing factors.Am. J. Transl. Res.20221485677568436105065
     [Google Scholar]
  74. de AraujoR.M.S. ObaY. KurodaS. TanakaE. MoriyamaK. RhoE regulates actin cytoskeleton organization in human periodontal ligament cells under mechanical stress.Arch. Oral Biol.201459218719210.1016/j.archoralbio.2013.11.01024370190
     [Google Scholar]
  75. GruenheidS. FinlayB.B. Microbial pathogenesis and cytoskeletal function.Nature2003422693377578110.1038/nature0160312700772
     [Google Scholar]
  76. YamamotoT. UgawaY. KawamuraM. YamashiroK. KochiS. IdeguchiH. TakashibaS. Modulation of microenvironment for controlling the fate of periodontal ligament cells: the role of Rho/ROCK signaling and cytoskeletal dynamics.J. Cell Commun. Signal.201812136937810.1007/s12079‑017‑0425‑329086204
     [Google Scholar]
  77. NoldeM. AlayashZ. ReckelkammS.L. KocherT. EhmkeB. HoltfreterB. BaurechtH. GeorgakisM.K. BaumeisterS.E. Downregulation of interleukin 6 signaling might reduce the risk of periodontitis: a drug target Mendelian randomization study.Front. Immunol.202314116014810.3389/fimmu.2023.116014837342352
     [Google Scholar]
  78. GórskaR. GregorekH. KowalskiJ. Laskus-PerendykA. SyczewskaM. MadalińskiK. Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis.J. Clin. Periodontol.200330121046105210.1046/j.0303‑6979.2003.00425.x15002890
     [Google Scholar]
  79. Yucel-LindbergT. BågeT. Inflammatory mediators in the pathogenesis of periodontitis.Expert Rev. Mol. Med.201315e710.1017/erm.2013.823915822
     [Google Scholar]
  80. DarveauR.P. CunninghamM.D. BaileyT. SeachordC. RatcliffeK. BainbridgeB. DietschM. PageR.C. AruffoA. Ability of bacteria associated with chronic inflammatory disease to stimulate E-selectin expression and promote neutrophil adhesion.Infect. Immun.19956341311131710.1128/iai.63.4.1311‑1317.19957534275
     [Google Scholar]
  81. SerhanC.N. ChiangN. Van DykeT.E. Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators.Nat. Rev. Immunol.20088534936110.1038/nri229418437155
     [Google Scholar]
  82. SupajaturaV. UshioH. NakaoA. AkiraS. OkumuraK. RaC. OgawaH. Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity.J. Clin. Invest.2002109101351135910.1172/JCI021470412021251
     [Google Scholar]
  83. FischerR.G. Gomes FilhoI.S. CruzS.S. OliveiraV.B. Lira-JúniorR. ScannapiecoF.A. RegoR.O. What is the future of periodontal medicine?Braz. Oral Res.202135Suppl. 2e10210.1590/1807‑3107bor‑2021.vol35.010234586216
     [Google Scholar]
  84. BaltaM.G. PapathanasiouE. BlixI.J. Van DykeT.E. Host modulation and treatment of periodontal disease.J. Dent. Res.2021100879880910.1177/002203452199515733655803
     [Google Scholar]
  85. GruberR. Molecular and cellular basis of bone resorption.Wien. Med. Wochenschr.20151653-4485310.1007/s10354‑014‑0310‑025223736
     [Google Scholar]
  86. TaubmanM.A. ValverdeP. HanX. KawaiT. Immune response: The key to bone resorption in periodontal disease.J. Periodontol.20057611S2033204110.1902/jop.2005.76.11‑S.2033
     [Google Scholar]
  87. HofbauerL.C. KhoslaS. DunstanC.R. LaceyD.L. BoyleW.J. RiggsB.L. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption.J. Bone Miner. Res.200015121210.1359/jbmr.2000.15.1.210646108
     [Google Scholar]
  88. JinQ. CirelliJ.A. ParkC.H. SugaiJ.V. TabaM.Jr KostenuikP.J. GiannobileW.V. RANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitis.J. Periodontol.20077871300130810.1902/jop.2007.07007317608585
     [Google Scholar]
  89. HajishengallisG. SahingurS.E. Novel inflammatory pathways in periodontitis.Adv. Dent. Res.2014261232910.1177/002203451452624024736701
     [Google Scholar]
  90. KawaiT. MatsuyamaT. HosokawaY. MakihiraS. SekiM. KarimbuxN.Y. GoncalvesR.B. ValverdeP. DibartS. LiY.P. MirandaL.A. ErnstC.W.O. IzumiY. TaubmanM.A. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease.Am. J. Pathol.2006169398799810.2353/ajpath.2006.06018016936272
     [Google Scholar]
  91. NagasawaT. KijiM. YashiroR. HormdeeD. LuH. KunzeM. SudaT. KoshyG. KobayashiH. OdaS. NittaH. IshikawaI. Roles of receptor activator of nuclear factor- κ B ligand (RANKL) and osteoprotegerin in periodontal health and disease.Periodontol. 20002007431658410.1111/j.1600‑0757.2006.00185.x17214836
     [Google Scholar]
  92. WankhedeA. WankhedeS. WasuS. Role of genetic in periodontal disease.J. ICDRO.2017925310.4103/jicdro.jicdro_10_17
     [Google Scholar]
  93. YoshieH. KobayashiT. TaiH. GaliciaJ.C. The role of genetic polymorphisms in periodontitis.Periodontol. 2000200743110213210.1111/j.1600‑0757.2006.00164.x17214838
     [Google Scholar]
  94. KinaneD.F. ShibaH. HartT.C. The genetic basis of periodontitis.Periodontol. 200020053919111710.1111/j.1600‑0757.2005.00118.x16135066
     [Google Scholar]
  95. MoutR. WillemzeR. LandegentJ.E. Repeat polymorphisms in the interleukin-4 gene (IL4).Nucleic Acids Res.19911913376310.1093/nar/19.13.37631804125
     [Google Scholar]
  96. SaxbyM. Prevalence of juvenile periodontitis in a British school population.Community Dent. Oral Epidemiol.198412318518710.1111/j.1600‑0528.1984.tb01435.x6589110
     [Google Scholar]
  97. ShapiraL. SchlesingerM. BimsteinE. Possible autosomal-dominant inheritance of prepubertal periodontitis in an extended kindred.J. Clin. Periodontol.199724638839310.1111/j.1600‑051X.1997.tb00202.x9205917
     [Google Scholar]
  98. ArchanaP.M. KumarT.S.S. PanishankarK.H. SalmanA.A. SaraswathiP.K. KumarasamyP. Association between interleukin-1 gene polymorphism and severity of chronic periodontitis in a South Indian population group.J. Indian Soc. Periodontol.201216217417810.4103/0972‑124X.9925823055581
     [Google Scholar]
  99. PeteanI.B.F. Silva-SousaA.C. CronenboldT.J. Mazzi-ChavesJ.F. SilvaL.A.B. SegatoR.A.B. CastroG.A.P. KuchlerE.C. Paula-SilvaF.W.G. Sousa-NetoM.D. Genetic, cellular and molecular aspects involved in apical periodontitis.Braz. Dent. J.202233411110.1590/0103‑644020220511336043561
     [Google Scholar]
  100. SakellariD. KoukoudetsosS. ArsenakisM. KonstantinidisA. Prevalence of IL-1A and IL-1B polymorphisms in a Greek population.J. Clin. Periodontol.2003301354110.1034/j.1600‑051X.2003.300106.x12702109
     [Google Scholar]
  101. HollaL.I. FassmannA. StejskalováA. ZnojilV. VaněkJ. VachaJ. Analysis of the interleukin-6 gene promoter polymorphisms in Czech patients with chronic periodontitis.J. Periodontol.2004751303610.1902/jop.2004.75.1.3015025214
     [Google Scholar]
  102. KomatsuY. TaiH. GaliciaJ.C. ShimadaY. EndoM. AkazawaK. YamazakiK. YoshieH. Interleukin-6 (IL-6) − 373 A9T11 allele is associated with reduced susceptibility to chronic periodontitis in Japanese subjects and decreased serum IL-6 level.Tissue Antigens200565111011410.1111/j.1399‑0039.2005.00347.x15663749
     [Google Scholar]
  103. NibaliL. Bayliss-ChapmanJ. AlmofarehS.A. ZhouY. DivarisK. VieiraA.R. What is the heritability of periodontitis? A systematic review.J. Dent. Res.201998663264110.1177/002203451984251031107142
     [Google Scholar]
  104. NCT04974502. U.S. National Library of Medicine.2021Available from: https://clinicaltrials.gov./study/NCT04974502?cond=Periodontitis&page=3&rank=21
  105. VokurkaJ. KlapušováL. PantuckovaP. KukletovaM. KuklaL. HollaL.I. The association of MMP-9 and IL-18 gene promoter polymorphisms with gingivitis in adolescents.Arch. Oral Biol.2009522172178
     [Google Scholar]
  106. KinaneD.F. Regulators of tissue destruction and homeostasis as diagnostic aids in periodontology.Periodontol.200024121522510.1034/j.1600‑0757.2000.2240110.x11276868
     [Google Scholar]
  107. LiW. ZhuY. SinghP. AjmeraD.H. SongJ. JiP. Association of common variants in MMPs with periodontitis risk.Dis. Markers20162016154597410.1155/2016/1545974
     [Google Scholar]
  108. SilvaN. AbuslemeL. BravoD. DutzanN. Garcia-SesnichJ. VernalR. HernándezM. GamonalJ. Host response mechanisms in periodontal diseases.J. Appl. Oral Sci.201523332935510.1590/1678‑77572014025926221929
     [Google Scholar]
  109. NasatzkyE. RubinsteinY. GoultschinJ. SchwartzZ. The role of Matrix Metaloproteinases in the progression of periodontitis, and the use of specific inhibitors to these enzymes in the treatment of the periodontal disease. Refu'at ha-peh veha-shinayim20032023845
     [Google Scholar]
  110. RyanM.E. RamamurthyS. GolubL.M. Matrix metalloproteinases and their inhibition in periodontal treatment.Curr. Opin. Periodontol.1996385968624573
     [Google Scholar]
  111. Chaussain-MillerC. FiorettiF. GoldbergM. MenashiS. The role of matrix metalloproteinases (MMPs) in human caries.J. Dent. Res.2006851223210.1177/15440591060850010416373676
     [Google Scholar]
  112. GroeninkJ. Walgreen-WeteringsE. NazmiK. BolscherJ.G.M. VeermanE.C.I. Van WinkelhoffA.J. Nieuw AmerongenA.V. Salivary lactoferrin and low- M r mucin MG2 in Actinobacillus actinomycetemcomitans -associated periodontitis.J. Clin. Periodontol.199926526927510.1034/j.1600‑051X.1999.260501.x10355615
     [Google Scholar]
  113. HelmerhorstE.J. OppenheimF.G. Saliva: a dynamic proteome.J. Dent. Res.200786868069310.1177/15440591070860080217652194
     [Google Scholar]
  114. KinneyJ.S. MorelliT. BraunT. RamseierC.A. HerrA.E. SugaiJ.V. ShelburneC.E. RayburnL.A. SinghA.K. GiannobileW.V. Saliva/pathogen biomarker signatures and periodontal disease progression.J. Dent. Res.201190675275810.1177/002203451139990821406610
     [Google Scholar]
  115. KaufmanE. LamsterI.B. Analysis of saliva for periodontal diagnosis.J. Clin. Periodontol.200027745346510.1034/j.1600‑051x.2000.027007453.x10914885
     [Google Scholar]
  116. HenskensY.M.C. VeermanE.C.I. MantelM.S. van der VeldenU. Nieuw AmerongenA.V. Cystatins S and C in human whole saliva and in glandular salivas in periodontal health and disease.J. Dent. Res.199473101606161410.1177/002203459407301005017929975
     [Google Scholar]
  117. VasudevanS. Role of saliva in periodontal health & disease-a review.Annals & Essences of Dentistry201134
     [Google Scholar]
  118. SyrjänenS. PiironenP. MarkkanenH. Free amino-acid content of wax-stimulated human whole saliva as related to periodontal disease.Arch. Oral Biol.198732960761010.1016/0003‑9969(87)90032‑X3481959
     [Google Scholar]
  119. PatilP. PatilB. Saliva: A diagnostic biomarker of periodontal diseases.J. Indian Soc. Periodontol.201115431031710.4103/0972‑124X.9256022368352
     [Google Scholar]
  120. KimJ.J. KimC.J. CamargoP.M. Salivary biomarkers in the diagnosis of periodontal diseases.J. Calif. Dent. Assoc.201341211912410.1080/19424396.2013.1222228523505757
     [Google Scholar]
  121. KeiserK. JohnsonC. TiptonD. Cytotoxicity of mineral trioxide aggregate using human periodontal ligament fibroblasts.J. Endod.200026528829110.1097/00004770‑200005000‑0001011199738
     [Google Scholar]
  122. SokosD. EvertsV. de VriesT.J. Role of periodontal ligament fibroblasts in osteoclastogenesis: A review.J. Periodontal Res.201550215215910.1111/jre.1219724862732
     [Google Scholar]
  123. de VriesT.J. SchoenmakerT. WattanaroonwongN. van den HoonaardM. NieuwenhuijseA. BeertsenW. EvertsV. Gingival fibroblasts are better at inhibiting osteoclast formation than periodontal ligament fibroblasts.J. Cell. Biochem.200698237038210.1002/jcb.2079516440316
     [Google Scholar]
  124. BloemenV. SchoenmakerT. de VriesT.J. EvertsV. Direct cell-cell contact between periodontal ligament fibroblasts and osteoclast precursors synergistically increases the expression of genes related to osteoclastogenesis.J. Cell. Physiol.2010222356557310.1002/jcp.2197119927302
     [Google Scholar]
  125. KookS.H. JangY.S. LeeJ.C. Human periodontal ligament fibroblasts stimulate osteoclastogenesis in response to compression force through TNF-α-mediated activation of CD4+ T cells.J. Cell. Biochem.2011112102891290110.1002/jcb.2320521618593
     [Google Scholar]
  126. KornmanK.S. Mapping the pathogenesis of periodontitis: A new look.J. Periodontol.2008798SSuppl.1560156810.1902/jop.2008.08021318673011
     [Google Scholar]
  127. ChappleI.L.C. MatthewsJ.B. The role of reactive oxygen and antioxidant species in periodontal tissue destruction.Periodontol. 2000200743116023210.1111/j.1600‑0757.2006.00178.x17214840
     [Google Scholar]
  128. KiyoshimaT. EnokiN. KobayashiI. SakaiT. NagataK. WadaH. FujiwaraH. OokumaY. SakaiH. Oxidative stress caused by a low concentration of hydrogen peroxide induces senescence-like changes in mouse gingival fibroblasts.Int. J. Mol. Med.20123051007101210.3892/ijmm.2012.110222922974
     [Google Scholar]
  129. KimS.C. KimO.S. KimO.J. KimY.J. ChungH.J. Antioxidant profile of whole saliva after scaling and root planing in periodontal disease.J. Periodontal Implant Sci.201040416417110.5051/jpis.2010.40.4.16420827325
     [Google Scholar]
  130. CanakçiC.F. CiçekY. CanakçiV. Reactive oxygen species and human inflammatory periodontal diseases.Biochemistry200570661962810.1007/s10541‑005‑0161‑916038603
     [Google Scholar]
  131. DemkovychA. BondarenkoY. HasiukP. Effects of quercetin on antioxidant potential in the experimental periodontitis development.Interv. Med. Appl. Sci.2019111606410.1556/1646.11.2019.0632148904
     [Google Scholar]
  132. KhudaF. BaharinB. AnuarN.N.M. SatiminB.S.F. NasruddinN.S. Effective modalities of periodontitis induction in rat model.J. Vet. Dent.2024411495710.1177/0898756423117845937259505
     [Google Scholar]
  133. LinP. NiimiH. OhsugiY. TsuchiyaY. ShimohiraT. KomatsuK. LiuA. ShibaT. AokiA. IwataT. KatagiriS. Application of ligature-induced periodontitis in mice to explore the molecular mechanism of periodontal disease.Int. J. Mol. Sci.20212216890010.3390/ijms2216890034445604
     [Google Scholar]
  134. MarchesanJ. GirnaryM.S. JingL. MiaoM.Z. ZhangS. SunL. MorelliT. SchoenfischM.H. InoharaN. OffenbacherS. JiaoY. An experimental murine model to study periodontitis.Nat. Protoc.201813102247226710.1038/s41596‑018‑0035‑430218100
     [Google Scholar]
  135. NCT04663165. U.S. National Library of Medicine.2020Available from: https://clinicaltrials.gov./study/NCT04663165?cond=Periodontitis&page=2&rank=12
  136. BaltacıoğluE. AkalınF.A. AlverA. BalabanF. ÜnsalM. KarabulutE. Total antioxidant capacity and superoxide dismutase activity levels in serum and gingival crevicular fluid in post-menopausal women with chronic periodontitis.J. Clin. Periodontol.200633638539210.1111/j.1600‑051X.2006.00923.x16677326
     [Google Scholar]
  137. Abou SulaimanA.E. ShehadehR.M.H. Assessment of total antioxidant capacity and the use of vitamin C in the treatment of non-smokers with chronic periodontitis.J. Periodontol.201081111547155410.1902/jop.2010.10017320569170
     [Google Scholar]
  138. BostanciV. TokerH. SenelS. OzdemirH. AydinH. Effect of chronic periodontitis on serum and gingival crevicular fluid oxidant and antioxidant status in patients with familial Mediterranean fever before and after periodontal treatment.J. Periodontol.201485570671210.1902/jop.2013.13023023826647
     [Google Scholar]
  139. AgnihotriR. PandurangP. KamathS.U. GoyalR. BallalS. ShanbhogueA.Y. KamathU. BhatG.S. BhatK.M. Association of cigarette smoking with superoxide dismutase enzyme levels in subjects with chronic periodontitis.J. Periodontol.200980465766210.1902/jop.2009.08054519335086
     [Google Scholar]
  140. TakaneM. SuganoN. IwasakiH. IwanoY. ShimizuN. ItoK. New biomarker evidence of oxidative DNA damage in whole saliva from clinically healthy and periodontally diseased individuals.J. Periodontol.200273555155410.1902/jop.2002.73.5.55112027259
     [Google Scholar]
  141. SheikhiM. BouhafsR.K.L. HammarströmK-J. JarstrandC. Lipid peroxidation caused by oxygen radicals from Fusobacterium -stimulated neutrophils as a possible model for the emergence of periodontitis.Oral Dis.200171414610.1034/j.1601‑0825.2001.70109.x11354921
     [Google Scholar]
  142. LoosB.G. CraandijkJ. HoekF.J. DillenP.M.E.W. Van Der VeldenU. Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients.J. Periodontol.200071101528153410.1902/jop.2000.71.10.152811063384
     [Google Scholar]
  143. SeinostG. WimmerG. SkergetM. ThallerE. BrodmannM. GasserR. BratschkoR.O. PilgerE. Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis.Am. Heart J.200514961050105410.1016/j.ahj.2004.09.05915976787
     [Google Scholar]
  144. GuravA.N. The implication of periodontitis in vascular endothelial dysfunction.Eur. J. Clin. Invest.201444101000100910.1111/eci.1232225104241
     [Google Scholar]
  145. TonettiM.S. D’AiutoF. NibaliL. DonaldA. StorryC. ParkarM. SuvanJ. HingoraniA.D. VallanceP. DeanfieldJ. Treatment of periodontitis and endothelial function.N. Engl. J. Med.2007356991192010.1056/NEJMoa06318617329698
     [Google Scholar]
  146. SuhJ.S. KimS. BoströmK.I. WangC.Y. KimR.H. ParkN.H. Periodontitis-induced systemic inflammation exacerbates atherosclerosis partly via endothelial–mesenchymal transition in mice.Int. J. Oral Sci.20191132110.1038/s41368‑019‑0054‑131257363
     [Google Scholar]
  147. SanzM. CerielloA. BuysschaertM. ChappleI. DemmerR. GrazianiF. HerreraD. JepsenS. LioneL. MadianosP. MathurM. MontanyaE. ShapiraL. TonettiM. VéghD. Scientific evidence on the links between periodontal diseases and diabetes: consensus report and guidelines of the joint workshop on periodontal diseases and by the international diabetes federation and the european federation of periodontology.Diabetes Res. Clin. Pract.2017201713729208508
     [Google Scholar]
  148. ShiB. LuxR. KlokkevoldP. ChangM. BarnardE. HaakeS. LiH. The subgingival microbiome associated with periodontitis in type 2 diabetes mellitus.ISME J.202014251953010.1038/s41396‑019‑0544‑331673077
     [Google Scholar]
  149. LiJ. LuH. WuH. HuangS. ChenL. GuiQ. ZhouW. YangY. WuY. ZhangH. ZhangQ. YangY. Periodontitis in elderly patients with type 2 diabetes mellitus: impact on gut microbiota and systemic inflammation.Aging20201224259562598010.18632/aging.20217433234730
     [Google Scholar]
  150. LallaE. PapapanouP.N. Diabetes mellitus and periodontitis: A tale of two common interrelated diseases.Nat. Rev. Endocrinol.201171273874810.1038/nrendo.2011.10621709707
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673302701240509103537
Loading
Hallmarks of Periodontitis
Curr. Med. Chem. 32, 2731 (2025); https://doi.org/10.2174/0109298673302701240509103537
/content/journals/cmc/10.2174/0109298673302701240509103537
/content/journals/cmc/10.2174/0109298673302701240509103537
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): alveolar bone resorption; genetic predisposition; immune response; inflammation; metabolic disorders; oxidative stress; pathogenic bacteria; Periodontal disease; risk factors

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test