Angiogenesis, Inflammation & Therapeutics | Impact 0.1 (CiteScore) | Online ISSN  2207-872X
REVIEWS   (Open Access)

Signaling Pathway Genetic Variations in Apical Periodontitis

Athira Ajith1, Usha Subbiah1*, Deepika. P2, Minthami Sharon P2

+ Author Affiliations

Journal of Angiotherapy 5(2) 1-6 https://doi.org/10.25163/angiotherapy.52214222315151221

Submitted: 23 November 2021  Revised: 26 November 2021  Published: 15 December 2021 

The purpose of this review is to provide information on host response and genetic variations in major apical periodontitis signaling pathways.

Abstract


Background: Apical periodontitis (AP) is a prevalent infectious disease characterized by inflammation and periradicular tissue loss, primarily induced by endodontic etiological agents. AP is the most common inflammatory lesion affecting teeth in the jaws, involving a complex interplay of cellular and molecular processes. Endogenous mediators, such as prostanoids, kinins, and neuropeptides, play a crucial role in the inflammatory response, which is further influenced by the host's immune response involving cytokines, proteases, and other pro-inflammatory mediators. Methods: This review synthesizes current research on the key signal transduction pathways involved in AP, focusing on the WNT, MAPK, NF-κB, JAK/STAT, and Notch signaling pathways. The genetic basis of AP is also explored, emphasizing the role of gene polymorphisms in disease susceptibility and progression. The review examines the differential expression of signaling molecules in AP tissues and their potential as therapeutic targets to modulate the host response and control disease progression. Results: The WNT/β-catenin pathway is implicated in osteoblast differentiation and bone resorption, with differential expression of WNT proteins observed in AP lesions. The MAPK pathway, particularly p38 MAPK, regulates inflammatory mediators and osteoclastogenesis, contributing to bone resorption in periapical lesions. NF-κB activation is significant in periodontally diseased tissues, and its inhibition has been shown to reduce periapical lesions and angiogenesis. The JAK/STAT pathway, particularly JAK2-STAT3, plays a critical role in immune regulation and cytokine signaling in AP. The Notch signaling pathway is involved in cell differentiation and inflammation, with its activation linked to pro-inflammatory cytokine expression in AP. Conclusion: The review highlights the complexity of the signaling networks involved in AP and the potential for targeting these pathways to modulate the inflammatory response and prevent tissue destruction.

Keywords: Apical periodontitis, Signaling pathways, WNT signaling, Genetic polymorphism, Inflammatory mediators

References


A. Aminoshariae and J. C. Kulild, 2015. "Association of functional gene polymorphism with apical periodontitis," J. Endod., vol. 41, no. 7, pp. 999-1007,
https://doi.org/10.1016/j.joen.2015.03.007

 
A. ElAyouti, M. I. Serry, J. Geis-Gerstorfer, and C. Löst, 2011 "Influence of cusp coverage on the fracture resistance of premolars with endodontic access cavities," Int. Endod. J., vol. 44, no. 6, pp. 543-549,.
https://doi.org/10.1111/j.1365-2591.2011.01859.x

 
A. R. De Sá et al., 2007 "Association of CD14, IL1B, IL6, IL10 and TNFA functional gene polymorphisms with symptomatic dental abscesses," Int. Endod. J., vol. 40, no. 7, pp. 563-572,
https://doi.org/10.1111/j.1365-2591.2007.01272.x

 
C. Peifer, G. Wagner, and S. Laufer, 2006. "New approaches to the treatment of inflammatory disorders small molecule inhibitors of p38 MAP kinase," Curr. Top. Med. Chem., vol. 6, no. 2, pp. 113-149,
https://doi.org/10.2174/156802606775270323

 
C. Zhang et al., 2019."JAK2/STAT3 is associated with the inflammatory process in periapical granuloma," Int. J. Clin. Exp. Pathol., vol. 12, no. 1, p. 190,
 
D. del Álamo, H. Rouault, and F. Schweisguth, 2011. "Mechanism and significance of cis-inhibition in Notch signalling," Curr. Biol., vol. 21, no. 1, pp. R40-R47,
https://doi.org/10.1016/j.cub.2010.10.034

 
E. A. Roberts, K. A. McCaffery, and S. M. Michalek, 1997. "Profile of cytokine mRNA expression in chronic adult periodontitis," J. Dent. Res., vol. 76, no. 12, pp. 1833-1839,
https://doi.org/10.1177/00220345970760120501

 
E. C. Küchler, J. F. Mazzi-Chaves, L. S. Antunes, C. Kirschneck, F. Baratto-Filho, and M. D. Sousa-Neto, 2018 "Current trends of genetics in apical periodontitis research," Braz. Oral Res., vol. 32,.
https://doi.org/10.1590/1807-3107bor-2018.vol32.0072

 
E. Karl et al., 2005. "Bcl-2 acts in a proangiogenic signaling pathway through nuclear factor-κB and CXC chemokines," Cancer Res., vol. 65, no. 12, pp. 5063-5069,
https://doi.org/10.1158/0008-5472.CAN-05-0140

 
G. L. Schieven, 2005."The biology of p38 kinase: a central role in inflammation," Curr. Top. Med. Chem., vol. 5, no. 10, pp. 921-928, [12] R. Zhang, L. Wang, and B. Peng, "Activation of p38 mitogen-activated protein kinase in rat periapical lesions," J. Endod., vol. 34, no. 10, pp. 1207-1210, 2008.
https://doi.org/10.1016/j.joen.2008.07.004

 
I. Ejaz and S. Ghafoor, 2019."WNT signalling pathway in oral lesions," JPMA,
https://doi.org/10.5455/JPMA.5890

 
J. A. C. de Souza, C. R. Junior, G. P. Garlet, A. V. B. Nogueira, and J. A. Cirelli, 2012 "Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease," J. Appl. Oral Sci., vol. 20, no. 2, pp. 128-138,.
https://doi.org/10.1590/S1678-77572012000200002

 
J. F. Siqueira Jr, I. N. Rôças, J. C. Provenzano, F. K. Daibert, M. G. Silva, and K. C. Lima, "Relationship between Fcγ receptor and interleukin-1 gene polymorphisms and post-treatment apical periodontitis," J. Endod., vol. 35, no. 9, pp. 1186-1192, 2009.
https://doi.org/10.1016/j.joen.2009.05.006

 
J. G. Walker et al., 2006. "Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid arthritis," Ann. Rheum. Dis., vol. 65, no. 2, pp. 149-156,
https://doi.org/10.1136/ard.2005.037929

 
J. López-López et al., 2012 "Tobacco smoking and radiographic periapical status: a retrospective case-control study," J. Endod., vol. 38, no. 5, pp. 584-588,.
https://doi.org/10.1016/j.joen.2012.02.011

 
J. N. Ihle and I. M. Kerr, 1995. "Jaks and Stats in signaling by the cytokine receptor superfamily," Trends Genet., vol. 11, no. 2, pp. 69-74,
https://doi.org/10.1016/S0168-9525(00)89000-9

 
L. C. de Souza et al., 2019. "WNT gene polymorphisms and predisposition to apical periodontitis," Sci. Rep., vol. 9, no. 1, pp. 1-9,
https://doi.org/10.1038/s41598-019-55293-6

 
M. E. Ryan, 1995 "Clinical applications for host modulatory therapy.," Compend. Contin. Educ. Dent. (Jamesburg, NJ), vol. 23, no. 11A, pp. 1071-1076, 2002.
 
M. J. B. Silva et al., 2011."The role of iNOS and PHOX in periapical bone resorption," J. Dent. Res., vol. 90, no. 4, pp. 495-500,
https://doi.org/10.1177/0022034510391792

 
M. Suzuki et al., 2000."The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-α-or IL-1β-stimulated rheumatoid synovial fibroblasts," FEBS Lett., vol. 465, no. 1, pp. 23-27,
https://doi.org/10.1016/S0014-5793(99)01717-2

 
P. F. Christopoulos, T. T. Gjølberg, S. Krüger, G. Haraldsen, J. T. Andersen, and E. Sundlisæter, 2021. "Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases," Front. Immunol., vol. 12,
https://doi.org/10.3389/fimmu.2021.668207

 
P. Stashenko, R. Teles, and R. d'Souza, 1998. "Periapical inflammatory responses and their modulation," Crit. Rev. Oral Biol. Med., vol. 9, no. 4, pp. 498-521, [2] I. Graunaite, G. Lodiene, and V. Maciulskiene, "Pathogenesis of apical periodontitis: a literature review," J. oral Maxillofac. Res., vol. 2, no. 4, 2011.
https://doi.org/10.5037/jomr.2011.2401

 
R. A. Backer et al., 2014. "A central role for Notch in effector CD8+ T cell differentiation," Nat. Immunol., vol. 15, no. 12, pp. 1143-1151,
https://doi.org/10.1038/ni.3027

 
R. Beyaert et al., 1996."The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor.," EMBO J., vol. 15, no. 8, pp. 1914-1923,
https://doi.org/10.1002/j.1460-2075.1996.tb00542.x

 
R. Starr and D. J. Hilton, 1999."Negative regulation of the JAK/STAT pathway," Bioessays, vol. 21, no. 1, pp. 47-52,
https://doi.org/10.1002/(SICI)1521-1878(199901)21:1<47::AID-BIES6>3.0.CO;2-N

 
R. Winzen et al., 1999."The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism," EMBO J., vol. 18, no. 18, pp. 4969-4980,
https://doi.org/10.1093/emboj/18.18.4969

 
S. Artavanis-Tsakonas, M. D. Rand, and R. J. Lake, 1999. "Notch signaling: cell fate control and signal integration in development," Science (80-. )., vol. 284, no. 5415, pp. 770-776,
https://doi.org/10.1126/science.284.5415.770

 
S. P. Tabruyn and A. W. Griffioen, 2008. "NF-κB: a new player in angiostatic therapy," Angiogenesis, vol. 11, no. 1, pp. 101-106,
https://doi.org/10.1007/s10456-008-9094-4

 
T. Berglundh and M. Donati, 2005. "Aspects of adaptive host response in periodontitis," J. Clin. Periodontol., vol. 32, pp. 87-107,
https://doi.org/10.1111/j.1600-051X.2005.00820.x

 
T. Kaneko et al., 2019. "Inhibition of nuclear factor kappa B prevents the development of experimental periapical lesions," J. Endod., vol. 45, no. 2, pp. 168-173,
https://doi.org/10.1016/j.joen.2018.10.006

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