TUMOR NECROSIS FACTOR-ALPHA A POTENTIAL THERAPEUTIC TARGET FOR PERIODONTITIS AND DIABETES MELLITUS

Authors

  • Angela Widjaja Universitas Gadjah Mada
  • Ahmad Syaify Universitas Gadjah Mada
  • Hendrawati Universitas Gadjah Mada

DOI:

https://doi.org/10.46862/interdental.v19i2.7706

Keywords:

Tumor necrosis factor-alpha, Periodontitis, Diabetes Melitus

Abstract

Introduction: Diabetes mellitus (DM) is a systemic disease that affects many human populations in the world. One of DM’s oral complications is periodontitis. The pro-inflammatory cytokine that plays a major role in the relationship between these two diseases is TNF-α.

Review: Diabetes mellitus is a systemic disease characterized by high blood glucose levels (hyperglycemia) due to inadequate insulin secretion, insulin resistance or both. Metabolic disorders caused by hyperglycemia can cause endothelial dysfunction in blood vessels. Endothelial dysfunction that occurs due to hyperglycemia can trigger an inflammatory response that can increase the progression of periodontitis. Periodontitis is a chronic inflammatory response in periodontal tissue to pathological microorganisms in dental biofilm. The periodontitis process begins with gingival inflammatory response. The initial phase of gingival inflammation is characterized by redness and bleeding on probing. Worsening inflammation will cause loss of periodontal tissue attachment and alveolar bone resorption which can lead to tooth loss. The inflammatory process that occurs in periodontitis involves pro-inflammatory cytokines that can influence insulin resistance, such as Tumor necrosis factor-alpha (TNF-α). Tumor necrosis factor-alpha is also a cytokine that plays a major role in the pathogenesis of diabetes mellitus, so that periodontitis and diabetes mellitus are interrelated diseases

Conclusion: The TNF-α cytokine is a potential therapy target for periodontitis and diabetes mellitus.

Downloads

Download data is not yet available.

References

Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022 Jan 1;183:109119. Available from: https://doi.org/10.1016/j.diabres.2021.109119

Ansari P, Choudhury ST, Seidel V, Rahman AB, Aziz MdA, Richi AE, et al. Therapeutic potential of quercetin in the management of type-2 diabetes mellitus. Life. 2022 Jul 28;12(8):1146. Available from: https://doi.org/10.3390/life12081146

Goyal R, Singhal M, Jialal I. Type 2 Diabetes. Treasure Island (FL): StatPearls Publishing; June 23, 2023.

Aoyama N, Suzuki J, Kobayashi N, Hanatani T, Ashigaki N, Yoshida A, et al. Increased Oral Porphyromonas gingivalis Prevalence in Cardiovascular Patients with Uncontrolled Diabetes Mellitus. Int Heart J. 2018 Jul 31;59(4):802–7. Available from: https://doi.org/10.1536/ihj.17-480

Newman MG, Takei H, Klokkevold PR, Carranza FA. Newman and Carranza’s Clinical Periodontology E-Book. 13th ed. Elsevier Health Sciences; 2018.

Kementerian Kesehatan Republik Indonesia, Laporan Nasional RISKESDAS. p: 207, 2018

Sari R, Herawati D, Nurcahyanti R, Wardani PK. Prevalensi periodontitis pada pasien diabetes mellitus (Studi observasional di poliklinik penyakit dalam RSUP Dr. Sardjito). Majalah Kedokteran Gigi Indonesia. 2017 Dec 7;3(2):98. Available from: https://doi.org/10.22146/majkedgiind.11241

Miyauchi M, Sato S, Kitagawa S, Hiraoka M, Kudo Y, Ogawa I, et al. Cytokine expression in rat molar gingival periodontal tissues after topical application of lipopolysaccharide. Histochem Cell Biol. 2001 Jul 1;116(1):57–62. Available from: https://doi.org/10.1007/s004180100298

Rhim EM, Park S, Kim DS, Kim S, Choi K, Choi GW. The effect of tumor necrosis factor (TNF)-α to induce matrix metalloproteinase (MMPs) from the human dental pulp, gingival, and periodontal ligament cells. J Korean Acad Conserv Dent. 2011 Jan 1;36(1):26. Available from: https://doi.org/10.5395/jkacd.2011.36.1.26

Karstoft K, Pedersen BK. Exercise and type 2 diabetes: focus on metabolism and inflammation. Immunol Cell Biol. 2015 Dec 1;94(2):146–50. Available from: https://doi.org/10.1038/icb.2015.101

Akash MSH, Rehman K, Liaqat A. Tumor necrosis Factor‐Alpha: Role in development of insulin resistance and pathogenesis of Type 2 diabetes mellitus. J Cell Biochem. 2017 Jun 22;119(1):105–10. Available from: https://doi.org/10.1002/jcb.26174

Hamed GMS, Selim M. Histological and Immunohistochemical study on the protective effect of Nano-selenium against experimental toxicity induced by Aflatoxin B1 (AFB1) on the gingiva and periodontal ligament of albino rats. Egypt Dent J. 2021 Jan 1;67(1):357–66. Available from: https://doi.org/10.21608/edj.2020.47103.1298

Natto ZS, Ahmad H, Alsharif LT, Alrowithi HF, Alsini DA, Salih HA, et al. Chronic Periodontitis Case Definitions and Confounders in Periodontal Research: A Systematic assessment. Biomed Res Int. 2018 Nov 28;2018:1–9. Available from: https://doi.org/10.1155/2018/4578782

Könönen E, Gürsoy M, Gürsoy UK. Periodontitis: a multifaceted disease of Tooth-Supporting tissues. J Clin Med. 2019 Jul 31;8(8):1135. Available from: https://doi.org/10.3390/jcm8081135

Hajishengallis G, Sahingur SE. Novel inflammatory pathways in periodontitis. Adv Dent Res. 2014 Apr 15;26(1):23–9. Available from: https://doi.org/10.1177/0022034514526240

Badanian A, Bueno L, Papone V. Análisis bacteriano comparativo de cuadros de Periodontitis Crónica y Agresiva en una población muestra de Uruguay. Odontoestomatología. 2019 Jun 1;21(33):5–13. Available from: https://doi.org/10.22592/ode2019n33a2

Hajishengallis G, Chavakis T, Lambris JD. Current understanding of periodontal disease pathogenesis and targets for host‐modulation therapy. Periodontology 2000. 2020 Aug 25;84(1):14–34. Available from: https://doi.org/10.1111/prd.12331

Mehrotra N, Singh S. Periodontitis. Treasure Island (FL): StatPearls Publishing; May 1, 2023.

Çekici A, Kantarcı A, Hastürk H, Van Dyke TE. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontology 2000. 2013 Dec 9;64(1):57–80. Available from: https://doi.org/10.1111/prd.12002

Martínez-García M, Hernández‐Lemus E. Periodontal Inflammation and Systemic Diseases: An Overview. Front Physiol. 2021 Oct 27;12. Available from: https://doi.org/10.3389/fphys.2021.709438

Kumar V, Arvina R, Sivaranjani K, Hema P, R AV. Role of Immunology in Periodontal Disease: A Brief review. Journal of Scientific Dentistry. 2018 Jan 1;8(2):25–8. Available from: https://doi.org/10.5005/jsd-8-2-25

Figueredo CM, Lira-Júnior R, Love RM. T and B Cells in Periodontal Disease: New Functions in A Complex Scenario. Int J Mol Sci. 2019 Aug 14;20(16):3949. Available from: https://doi.org/10.3390/ijms20163949

Friedmann A, Özmeriç N, Bernimoulin J, Kleber B, Ayhan E, Aykan T, et al. Clinical immunology Receptor activator of NF-kappaB ligand (RANKL) and CD 31 expressions in chronic periodontitis patients before and after surgery. Cent Eur J Immunol. 2014 Jan 1;4:508–17. Available from: https://doi.org/10.5114/ceji.2014.47737

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 Jan 1;2014:1–7. Available from: https://doi.org/10.1155/2014/731039

Standards of Medical Care in Diabetes—2015 abridged for primary care providers. Clinical Diabetes [Internet]. 2015 Apr 1;33(2):97–111. Available from: https://doi.org/10.2337/diaclin.33.2.97

Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami R. Type 2 Diabetes and its Impact on the Immune System. Curr Diabetes Rev. 2020 May 12;16(5):442–9. Available from: https://doi.org/10.2174/1573399815666191024085838

Bhat S, Mary S, Giri AP, Kulkarni MJ. Advanced glycation End Products (AGEs) in diabetic complications. In: Springer eBooks. 2017. p. 423–49. Available from: https://doi.org/10.1007/978-3-319-60324-7_19

Nowotny K, Jung T, Höhn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules. 2015 Mar 16;5(1):194–222. Available from: https://doi.org/10.3390/biom5010194

Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol. 2014 Jan 1;18(1):1. Available from: https://doi.org/10.4196/kjpp.2014.18.1.1

Prasad K, Mishra M. AGE–RAGE Stress, stressors, and antistressors in health and disease. Int J Angiol. 2017 Dec 28;27(01):001–12. Available from: https://doi.org/10.1055/s-0037-1613678

Volpe CMO, Villar-Delfino PH, Anjos PMFD, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis. 2018 Jan 25;9(2). Available from: https://doi.org/10.1038/s41419-017-0135-z

Asmat U, Khan AR, Koçyiğit İ. Diabetes mellitus and oxidative stress—A concise review. Saudi Pharmaceutical Journal. 2016 Sep 1;24(5):547–53. Available from: https://doi.org/10.1016/j.jsps.2015.03.013

Van Der Velde AR, Meijers WC, De Boer RA. Cardiovascular biomarkers. In: Elsevier eBooks. 2015. p. 167–83. Available from: https://doi.org/10.1016/b978-0-12-800687-0.00018-9

Choubaya C, Chahine N, Aoun G, Anil S, Zalloua P, Salameh Z. Expression of Inflammatory Mediators in Periodontitis Over Established Diabetes: an Experimental Study in Rats. Medicinski Arhiv. 2021 Jan 1;75(6):436. Available from: https://doi.org/10.5455/medarh.2021.75.436-443

Molina CA, Ojeda LF, Jiménez MS, Portillo CM, Olmedo IS, Hernández TM, et al. Diabetes and Periodontal Diseases: An Established Two-Way relationship. Journal of Diabetes Mellitus. 2016 Jan 1;06(04):209–29. Available from: https://doi.org/10.4236/jdm.2016.64024

Stanimirović J, Radovanović J, Banjac K, Obradović M, Essack M, Zafirović S, et al. Role of C-Reactive protein in diabetic inflammation. Mediators of Inflammation. 2022 May 17;2022:1–15. Available from: https://doi.org/10.1155/2022/3706508

Cavalla F, Patricia HR, Sorsa T, Claudia B, Hernández M. Matrix metalloproteinases as regulators of periodontal inflammation. Int J Mol Sci. 2017 Feb 17;18(2):440. Available from: https://doi.org/10.3390/ijms18020440

Rehman K, Akash MSH. Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? J Biomed Sci. 2016 Dec 1;23(1). Available from: https://doi.org/10.1186/s12929-016-0303-y

Santoso O. Infeksi Periodontal Sebagai Faktorrisiko Kondisi Sistemik. Odonto: Dental Journal. 2019 Dec 31; Available from: https://doi.org/10.30659/odj.6.2.141-152

Ma C, Yu H, Xiao Y, Wang H. Momordica charantia extracts ameliorate insulin resistance by regulating the expression of SOCS-3 and JNK in type 2 diabetes mellitus rats. Pharm Biol. 2017 Jan 1;55(1):2170–7. Available from: https://doi.org/10.1080/13880209.2017.1396350

Kim JH, Lee D, Woo GH, Heon J, Bak E, Yoo Y. Osteocytic sclerostin expression in alveolar bone in rats with diabetes mellitus and Ligature-Induced periodontitis. J Periodontol. 2015 Aug 1;86(8):1005–11. Available from: https://doi.org/10.1902/jop.2015.150083

Jiang Z, Cui Y, Gao R, Li Y, Fu Z, Zhang B, et al. Study of TNF-α, IL-1β and LPS levels in the gingival crevicular fluid of a rat model of diabetes mellitus and periodontitis. DOAJ (DOAJ: Directory of Open Access Journals). 2013 Jan 1; Available from: https://doaj.org/article/8c371d89281441969de1ef602817e52d

Okada H, Murakami S. Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med. 1998 Jul 1;9(3):248–66. Available from: https://doi.org/10.1177/10454411980090030101

Singh P, Gupta ND, Bey A, Khan S. Salivary TNF-alpha: A potential marker of periodontal destruction. Journal of Indian Society of Periodontology. 2014 Jan 1;18(3):306. Available from: https://doi.org/10.4103/0972-124x.134566

Radhika B, Appukuttan D, Prakash PSG, Subramanian S, Victor DJ, Balasundaram A. Estimation of Periostin and Tumour Necrosis Factor-α in Type II Diabetics with Chronic Periodontitis: A case–control study. Journal of Indian Society of Periodontology. 2019 Jan 1;23(2):106. Available from: https://doi.org/10.4103/jisp.jisp_397_18

Berniyanti T, Wening GRS, Palupi R, Setyowati D, Putri CR. Low Levels of Tumor Necrosis Factor-α will Prevent Periodontitis Exacerbation in Type 2 Diabetes Mellitus. Eur J Dent. 2022 Jan 11;16(02):443–8. Available from: https://doi.org/10.1055/s-0041-1739442

Bakshi D, Kaur G, Singh D, Sahota JK, Thakur A, Grover S. Estimation of Plasma Levels of Tumor Necrosis Factor-α, Interleukin-4 and 6 in Patients with Chronic Periodontitis and Type II Diabetes Mellitus. J Contemp Dent Pract. 2018 Jan 1;19(2):166–9. Available from: https://doi.org/10.5005/jp-journals-10024-2231

Kurniati F, Masulili SLC, Haerani N, Tadjoedin FM, Harsas NA, Soedarsono N et al. Level of Tumor Necrosis Factor Alpha in Elderly Patients with Periodontitis and Diabetes Mellitus. J Int Dent Medical Res. 2020;13(4):1461-1466

Swetaa A, Jeevitha M, Jayaraman S. Measurement of Salivary Tumor Necrosis Factor- alpha (TNF- α) in Periodontitis Patients with or without Diabetes Mellitus. J Pharm Res Int. 2021 Dec 29;1–7. Available from: https://doi.org/10.9734/jpri/2021/v33i62b35163

Loo G, Bertrand MJM. Death by TNF: a road to inflammation. Nat Rev Immunology. 2022 Nov 15;23(5):289–303. Available from: https://doi.org/10.1038/s41577-022-00792-3

Atzeni F, Sarzi‐Puttini P. Tumor necrosis factor. In: Elsevier eBooks [Internet]. 2013. p. 229–31. Available from: https://doi.org/10.1016/b978-0-12-374984-0.01594-1

Idriss HT, Naismith JH. TNF? and the TNF receptor superfamily: Structure-function relationship(s). Microsc Res Tech. 2000 Jan 1;50(3):184–95. Available from: https://doi.org/10.1002/1097-0029(20000801)50:3<184::aid-jemt2>3.0.co;2-h

Du Yan S, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou Y, et al. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem. 1994 Apr 1;269(13):9889–97. Available from: https://doi.org/10.1016/s0021-9258(17)36966-1

Griffin DE. Cytokines and Chemokines. In: Elsevier eBooks. 1999. p. 339–44. Available from: https://doi.org/10.1006/rwvi.1999.0062

Yang S, Wang J, Brand D, Zheng SG. Role of TNF–TNF receptor 2 signal in regulatory T cells and its therapeutic implications. Front Immunol. 2018 Apr 19;9. Available from: https://doi.org/10.3389/fimmu.2018.00784

Parameswaran N, Patial S. Tumor necrosis factor-Α signaling in macrophages. Crit Rev Eukaryot Gene Expr. 2010 Jan 1;20(2):87–103. Available from: https://doi.org/10.1615/critreveukargeneexpr.v20.i2.10

Kibune R, Muraoka K, Morishita M, Ariyoshi W, Awano S. Relationship between Dynamics of TNF-α and Its Soluble Receptors in Saliva and Periodontal Health State. Dentistry Journal. 2022 Feb 8;10(2):25. Available from: https://doi.org/10.3390/dj10020025

Noh MK, Jung MH, Kim SH, Lee SR, Park KH, Kim DH, et al. Assessment of IL-6, IL-8 and TNF-α levels in the gingival tissue of patients with periodontitis. Exp Ther Med. 2013 Jul 15;6(3):847–51. Available from: https://doi.org/10.3892/etm.2013.1222

Bunjaku V, Popovska M, Todoroska S, Rusevska B, Cana A, Spasovski S, & Spasovska-Gjorgovska A. The Role of TNF-Α in Saliva and Gingival Fluid in Patients with Chronic Periodontitis and Type 2 Diabetes. J Int Dent Med Res. 2021; 14(2): 671-679

Savira A, Mujayanto R, Amurwaningsih M. Bay Leaf (Syzygium polyanthum) Extract Gel Effect on TNF-Α Expression In Traumatic Ulcers Healing Process. Odonto: Dental Journal. 2020 Aug 5;7(1):25. Available from: https://doi.org/10.30659/odj.7.1.25-30

Nilsson J, Jovinge S, Niemann A, Reneland R, Lithell H. Relation between plasma tumor necrosis factor-Α and insulin sensitivity in elderly men with Non–Insulin-Dependent diabetes mellitus. Arterioscler Thromb Vasc Biol. 1998 Aug 1;18(8):1199–202. Available from: https://doi.org/10.1161/01.atv.18.8.1199

Pulivarthi P, Chava VK, Gunupati S. Salivary tumor necrosis factor-alpha levels in periodontitis associated with diabetes mellitus after low level laser therapy as an adjunct to scaling and root planning: A randomized clinical trial. Journal of Indian Society of Periodontology. 2022 Jan 1;26(3):236. Available from: https://doi.org/10.4103/jisp.jisp_150_21

Downloads

Published

2023-12-23

How to Cite

1.
Widjaja A, Syaify A, Hendrawati. TUMOR NECROSIS FACTOR-ALPHA A POTENTIAL THERAPEUTIC TARGET FOR PERIODONTITIS AND DIABETES MELLITUS . interdental [Internet]. 2023 Dec. 23 [cited 2024 Apr. 29];19(2):148-57. Available from: https://e-journal.unmas.ac.id/index.php/interdental/article/view/7706