The role of Treponema denticola in the periodontitis alveolar bone damage: Systematic review

Erik Idrus, Willy Hartanto, Widya Lestari, Dewi Fatma Suniarti


Background: Periodontitis is a chronic inflammation condition of the periodontal tissue, which causes irreversible, progressive deterioration of the tooth-supporting tissue, leading to tooth loss. One of the main bacteria in the pathogenesis of periodontitis is Treponema denticola. Its involvement in periodontitis includes producing and releasing various virulence factors that further modulate inflammation and ignite alveolar bone destruction. Objective: To examine Treponema denticola's role in the mechanism of alveolar bone damage in periodontitis. Method: This systematic review was conducted from August 2021 until April 2022. Qualified literature is evaluated based on inclusion criteria, including published in English within the last ten years and research articles available in full text. The inclusion literature’s determination was based on the PRISMA (Preferred Reporting Item for Systematic Review and Meta-Analysis). Result: Six journals fit the inclusion criteria and discuss Treponema denticola involvement in alveolar bone destruction via several mechanisms, including periplasmic flagella as its virulence factor. Treponema denticola can inhibit osteogenic cell differentiation and induce the production TNF-α, IL-6, and IL-1β, which are the proinflammatory cytokines involved in osteoclastogenesis. The induction mechanism of these various cytokines can ultimately increase osteoclast differentiation by increasing RANKL expression and decreasing OPG expression. Conclusion: Treponema denticola is involved in alveolar bone destruction by inhibiting bone formation and inducing an inflammatory response in immune cells that can increase osteoclast differentiation, as observed in alveolar bone destruction.


Treponema denticola; periodontitis; bone damage; bone cells

Full Text:



Cheng WC, van Asten SD, Burns LA, Evans HG, Walter GJ, Hashim A, et al. Periodontitis-associated pathogens P. gingivalis and A. actinomycetemcomitans activate human CD14(+) monocytes leading to enhanced Th17/IL-17 responses. Eur J Immunol. 2016;46(9):2211-21.

Kwon T, Lamster IB, Levin L. Current Concepts in the Management of Periodontitis. Int Dent J. 2021 ;71(6):462-76.

Albuquerque-Souza E, Sahingur SE. Periodontitis, chronic liver diseases, and the emerging oral-gut-liver axis. Periodontol 2000. 2022;89(1):125-41.

Parsegian K, Randall D, Curtis M, Ioannidou E. Association between periodontitis and chronic kidney disease. Periodontol 2000. 2022;89(1):114-24.

Larsen T, Fiehn NE. Dental biofilm infections - an update. APMIS. 2017;125(4):376-84.

Cekici A, Kantarci A, Hasturk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000. 2014;64(1):57-80.

Chen B, Wu W, Sun W, Zhang Q, Yan F, Xiao Y. RANKL expression in periodontal disease: where does RANKL come from? Biomed Res Int. 2014;2014:731039.

Dashper SG, Seers CA, Tan KH, Reynolds EC. Virulence factors of the oral spirochete Treponema denticola. J Dent Res. 2011;90(6):691-703.

Hienz SA, Paliwal S, Ivanovski S. Mechanisms of Bone Resorption in Periodontitis. J Immunol Res. 2015;2015:615486.

Kim JH, Kim N. Signaling Pathways in Osteoclast Differentiation. Chonnam Med J. 2016;52(1):12-7.

Krauss JL, Roper PM, Ballard A, Shih CC, Fitzpatrick JAJ, Cassat JE, et al. Staphylococcus aureus Infects Osteoclasts and Replicates Intracellularly. mBio. 2019;10(5):e02447-19.

Miao D, Godovikova V, Qian X, Seshadrinathan S, Kapila YL, Fenno JC. Treponema denticola upregulates MMP-2 activation in periodontal ligament cells: interplay between epigenetics and periodontal infection. Arch Oral Biol. 2014;59(10):1056-64.

Muka T, Glisic M, Milic J, Verhoog S, Bohlius J, Bramer W, et al. A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research. Eur J Epidemiol. 2020;35(1):49-60.

Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Open Med. 2009;3(3):e123-30.

Xu J, Gong T, Heng BC, Zhang CF. A systematic review: differentiation of stem cells into functional pericytes. FASEB J. 2017;31(5):1775-86.

Ruby J, Martin M, Passineau MJ, Godovikova V, Fenno JC, Wu H. Activation of the innate immune system by Treponema denticola periplasmic flagella through Toll-like receptor 2. Infect Immun. 2017;86(1):e00573-17.

Chow AT, Quah SY, Bergenholtz G, Lim KC, Yu VSH, Tan KS. Bacterial species associated with persistent apical periodontitis exert differential effects on osteogenic differentiation. Int Endod J. 2019;52(2):201-10.

Cecil JD, O'Brien-Simpson NM, Lenzo JC, Holden JA, Singleton W, Perez-Gonzalez A, et al. Outer membrane vesicles prime and activate macrophage inflammasomes and cytokine secretion in vitro and in vivo. Front Immunol. 2017;8:1017.

Ramenzoni LL, Russo G, Moccia MD, Attin T, Schmidlin PR. Periodontal bacterial supernatants modify differentiation, migration and inflammatory cytokine expression in human periodontal ligament stem cells. PLoS One. 2019;14(7):e0219181.

Yucel-Lindberg T, Bage T. Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med. 2013;15:e7.

Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol. 2014;35(1):3-11.

Maurizi A, Rucci N. The Osteoclast in Bone Metastasis: Player and Target. Cancers (Basel). 2018;10(7):218.

Soysa NS, Alles N, Aoki K, Ohya K. Osteoclast formation and differentiation: an overview. J Med Dent Sci. 2012;59(3):65-74.

Kikuchi Y, Kimizuka R, Kato T, Okuda K, Kokubu E, Ishihara K. Treponema denticola Induces Epithelial Barrier Dysfunction in Polarized Epithelial Cells. Bull Tokyo Dent Coll. 2018;59(4):265-75.

Visser MB, Ellen RP. New insights into the emerging role of oral spirochaetes in periodontal disease. Clin Microbiol Infect. 2011;17(4):502-12.

Asai Y, Jinno T, Ogawa T. Oral treponemes and their outer membrane extracts activate human gingival epithelial cells through toll-like receptor 2. Infect Immun. 2003;71(2):717-25.

Hinson AN, Hawkes CG, Blake CS, Fitzsimonds ZR, Zhu B, Buck G, Lamont RJ, Miller DP. Treponema denticola Induces Interleukin-36γ Expression in Human Oral Gingival Keratinocytes via the Parallel Activation of NF-κB and Mitogen-Activated Protein Kinase Pathways. Infect Immun. 2022;90(10):e0024722.

Ganther S, Radaic A, Malone E, Kamarajan P, Chang NN, Tafolla C, Zhan L, Fenno JC, Kapila YL. Treponema denticola dentilisin triggered TLR2/MyD88 activation upregulates a tissue destructive program involving MMPs via Sp1 in human oral cells. PLoS Pathog. 2021;17(7):e1009311.

Malone ET, Ganther S, Mena N, Radaic A, Shariati K, Kindberg A, Tafolla C, Kamarajan P, Fenno JC, Zhan L, Kapila YL. Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction and MMP-2 Activity in Periodontal Fibroblasts. Front Cell Infect Microbiol. 2021;11:671968.

Petain S, Kasnak G, Firatli E, Tervahartiala T, Gürsoy UK, Sorsa T. Periodontitis and peri-implantitis tissue levels of Treponema denticola-CTLP and its MMP-8 activating ability. Acta Histochem. 2021;123(6):151767.

Jones MM, Vanyo ST, Ibraheem W, Maddi A, Visser MB. Treponema denticola stimulates Oncostatin M cytokine release and de novo synthesis in neutrophils and macrophages. J Leukoc Biol. 2020;108(5):1527-41.

Lim Y, Kim HY, An SJ, Choi BK. Activation of bone marrow-derived dendritic cells and CD4+ T cell differentiation by outer membrane vesicles of periodontal pathogens. J Oral Microbiol. 2022;14(1):2123550.

Kim M, Jun HK, Choi BK, Cha JH, Yoo YJ. Td92, an outer membrane protein of Treponema denticola, induces osteoclastogenesis via prostaglandin E(2)-mediated RANKL/osteoprotegerin regulation. J Periodontal Res. 2010;45:772–9.



  • There are currently no refbacks.

Lisensi Creative Commons
This work is licensed under a Lisensi Creative Commons Atribusi-BerbagiSerupa 4.0 Internasional.
Contact us: Odonto Dental Journal: Jl. Raya Kaligawe Km.4, PO BOX 1054/SM Semarang, Central Java, Indonesia, 50112. Email: