Current Understanding of Periodontal Disease Pathogenesis and Targets for Host-modulation Therapy

Overview

Journal Periodontol 2000

Date 2020 Aug 27

PMID 32844416

Citations 151

Authors

George Hajishengallis

Triantafyllos Chavakis

John D Lambris

Affiliations

Soon will be listed here.

Abstract

Recent advances indicate that periodontitis is driven by reciprocally reinforced interactions between a dysbiotic microbiome and dysregulated inflammation. Inflammation is not only a consequence of dysbiosis but, via mediating tissue dysfunction and damage, fuels further growth of selectively dysbiotic communities of bacteria (inflammophiles), thereby generating a self-sustained feed-forward loop that perpetuates the disease. These considerations provide a strong rationale for developing adjunctive host-modulation therapies for the treatment of periodontitis. Such host-modulation approaches aim to inhibit harmful inflammation and promote its resolution or to interfere directly with downstream effectors of connective tissue and bone destruction. This paper reviews diverse strategies targeted to modulate the host periodontal response and discusses their mechanisms of action, perceived safety, and potential for clinical application.

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References

Thorbert-Mros S, Larsson L, Berglundh T . Cellular composition of long-standing gingivitis and periodontitis lesions. J Periodontal Res. 2014; 50(4):535-43. DOI: 10.1111/jre.12236. View

Salvi G, Lang N . The effects of non-steroidal anti-inflammatory drugs (selective and non-selective) on the treatment of periodontal diseases. Curr Pharm Des. 2005; 11(14):1757-69. DOI: 10.2174/1381612053764878. View

Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, Nagata S . Identification of a factor that links apoptotic cells to phagocytes. Nature. 2002; 417(6885):182-7. DOI: 10.1038/417182a. View

Ricklin D, Lambris J . Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013; 190(8):3831-8. PMC: 3623009. DOI: 10.4049/jimmunol.1203487. View

Chen C . COX-2's new role in inflammation. Nat Chem Biol. 2010; 6(6):401-2. DOI: 10.1038/nchembio.375. View

Netea M, Joosten L, Latz E, Mills K, Natoli G, Stunnenberg H . Trained immunity: A program of innate immune memory in health and disease. Science. 2016; 352(6284):aaf1098. PMC: 5087274. DOI: 10.1126/science.aaf1098. View

Serhan C . Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014; 510(7503):92-101. PMC: 4263681. DOI: 10.1038/nature13479. View

Neves J, Sousa-Victor P, Jasper H . Rejuvenating Strategies for Stem Cell-Based Therapies in Aging. Cell Stem Cell. 2017; 20(2):161-175. PMC: 5681350. DOI: 10.1016/j.stem.2017.01.008. View

Baron R, Ferrari S, Russell R . Denosumab and bisphosphonates: different mechanisms of action and effects. Bone. 2010; 48(4):677-92. DOI: 10.1016/j.bone.2010.11.020. View

10.

Wagner W, Horn P, Bork S, Ho A . Aging of hematopoietic stem cells is regulated by the stem cell niche. Exp Gerontol. 2008; 43(11):974-80. DOI: 10.1016/j.exger.2008.04.007. View

11.

Hanayama R, Tanaka M, Miwa K, Nagata S . Expression of developmental endothelial locus-1 in a subset of macrophages for engulfment of apoptotic cells. J Immunol. 2004; 172(6):3876-82. DOI: 10.4049/jimmunol.172.6.3876. View

12.

Hong C, Kidani Y, A-Gonzalez N, Phung T, Ito A, Rong X . Coordinate regulation of neutrophil homeostasis by liver X receptors in mice. J Clin Invest. 2011; 122(1):337-47. PMC: 3248291. DOI: 10.1172/JCI58393. View

13.

Armitage G . Periodontal diagnoses and classification of periodontal diseases. Periodontol 2000. 2004; 34:9-21. DOI: 10.1046/j.0906-6713.2002.003421.x. View

14.

Lajoie S, Lewkowich I, Suzuki Y, Clark J, Sproles A, Dienger K . Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol. 2010; 11(10):928-35. PMC: 2943538. DOI: 10.1038/ni.1926. View

15.

Kassebaum N, Bernabe E, Dahiya M, Bhandari B, Murray C, Marcenes W . Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dent Res. 2014; 93(11):1045-53. PMC: 4293771. DOI: 10.1177/0022034514552491. View

16.

Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R . Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010; 329(5990):454-7. PMC: 3132938. DOI: 10.1126/science.1188280. View

17.

Mira A, Simon-Soro A, Curtis M . Role of microbial communities in the pathogenesis of periodontal diseases and caries. J Clin Periodontol. 2017; 44 Suppl 18:S23-S38. DOI: 10.1111/jcpe.12671. View

18.

Flannagan R, Canton J, Furuya W, Glogauer M, Grinstein S . The phosphatidylserine receptor TIM4 utilizes integrins as coreceptors to effect phagocytosis. Mol Biol Cell. 2014; 25(9):1511-22. PMC: 4004599. DOI: 10.1091/mbc.E13-04-0212. View

19.

Allaker R, Stephen A . Use of Probiotics and Oral Health. Curr Oral Health Rep. 2017; 4(4):309-318. PMC: 5688201. DOI: 10.1007/s40496-017-0159-6. View

20.

Mizutani N, Goshima H, Nabe T, Yoshino S . Complement C3a-induced IL-17 plays a critical role in an IgE-mediated late-phase asthmatic response and airway hyperresponsiveness via neutrophilic inflammation in mice. J Immunol. 2012; 188(11):5694-705. DOI: 10.4049/jimmunol.1103176. View