Human Beta-defensin-1 and Periodontal Disease: The Past, Present, and Future

  • Benso Sulijaya Department of Periodontology, Faculty of Dentistry, Universitas Indonesia, Indonesia
  • Sri Lelyati C Masulili Dental Division, Universitas Indonesia Hospital, Indonesia
  • Elza Ibrahim Auerkari Department of Oral Biology, Faculty of Dentistry, Universitas Indonesia. Indonesia


Human beta-defensin-1 (HBD-1), a peptide released by the immune system, has been investigated for its association with periodontal disease. Several studies have found positive findings of its expression related to disease progression, whereas others have reported some tendencies. This review highlights studies associated with HBD-1 and periodontal disease in both primary and clinical investigations, as well as the underlying mechanism and discusses further research possibilities for HBD-1. HBD-1 acts as an innate immune apparatus and mediating the adaptive immune system; therefore, its role in the pathogenesis of a periodontal disease is indisputable. HBD-1 is mainly expressed in the oral stratified epithelium and sulcular epithelium, where the barrier junction properties (e.g., E-cadherin and β-catenin in the adherent junction) of the gingival epithelial cells serve as the first line of defense against periodontal infection. The HBD-1-reinforced epithelium therefore provides both a mechanical and a chemical barrier action. Critical issues that arise in the gingival epithelium can therefore be alleviated by modulation of HBD-1 production to enhance its protective function. The antimicrobial, anti-inflammatory, and wound healing properties of HBD-1 support its use as a promising clinical treatment strategy.


Dale BA, Fredericks LP. Antimicrobial peptides in the oral environment: Expression and function in health and disease. Curr Issues Mol Biol. 2005;7:119–34.
Gursoy UK, Könönen E. Understanding the roles of gingival beta-defensins. J Oral Microbiol. 2012;4:1-10.
Huttner KM, Bevins CL. Antimicrobial peptides as mediators of epithelial host defense. Pediatr Res. 1999;45:785–94.
Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, et al. Discovery of five conserved beta -defensin gene clusters using a computational search strategy. Proc Natl Acad Sci U S A. 2002;99(4):2129-33.
Dale BA. Periodontal epithelium: A newly recognized role in health and disease. Periodontol 2000. 2002;30:70–78.
Dale BA, Fredericks LP, Dale BA, Biology O. Antimicrobial peptides in the oral environment : expression and function in health and disease. Curr Issues Mol Biol. 2003;7:119–134.
Vardar-Sengul S, Demirci T, Sen BH, Erkizan V, Kurulgan E, Baylas H. Human beta defensin-1 and -2 expression in the gingiva of patients with specific periodontal diseases. J Periodontal Res. 2007;42(5):429-37.
Raschig J, Mailänder-Sánchez D, Berscheid A, Berger J, Strömstedt AA, Courth LF, et al. Ubiquitously expressed Human Beta Defensin 1 (hBD1) forms bacteria-entrapping nets in a redox dependent mode of action. PLoS Pathog. 2017;13(3):e1006261.
Lu Q, Jin L, Darveau RP, Samaranayake LP. Expression of human beta-defensins-1 and -2 peptides in unresolved chronic periodontitis. J Periodontal Res. 2004;39(4):221-7.
Sulijaya B, Masulili SRILC, Lessang R, Soeroso Y, Auerkari EI. The human beta-defensin-1 level from smokers with chronic periodontitis. Asian J Pharm Clin Res. 2016;9:174–6.
Ertugrul AS, Dikilitas A, Sahin H, Alpaslan N, Bozoglan A, Tekin Y. Gingival crevicular fluid levels of human beta-defensins 1 and 3 in subjects with periodontitis and/or type 2 diabetes mellitus: a cross-sectional study. J Periodontal Res. 2013;48(4):475-82.
Liu J, Chen J, Du X, Hu L, Chen L. The expression of hBDs in the gingival tissue and keratinocytes from healthy subjects and periodontitis patients. Arch Oral Biol. 2014;59(2):193-8.
Wang P, Duan D, Zhou X, Li X, Yang J, Deng M, et al. Relationship between expression of human gingival beta-defensins and levels of periodontopathogens in subgingival plaque. J Periodontal Res. 2015;50(1):113-22.
Li X, Duan D, Yang J, Wang P, Han B, Zhao L, et al. The expression of human β-defensins (hBD-1, hBD-2, hBD-3, hBD-4) in gingival epithelia. Arch Oral Biol. 2016;66:15-21.
Hollox EJ, Armour JA, Barber JC. Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster. Am J Hum Genet. 2003;73(3):591-600.
Schaefer AS, Richter GM, Nothnagel M, Laine ML, Rühling A, Schäfer C, et al. A 3' UTR transition within DEFB1 is associated with chronic and aggressive periodontitis. Genes Immun. 2010;11(1):45-54.
Ozturk A, Famili P, Vieira AR. The antimicrobial peptide DEFB1 is associated with caries. J Dent Res. 2010 Jun;89(6):631-6.
Ikuta T, Inagaki Y, Tanaka K, Saito T, Nakajima Y, Bando M, et al. Gene polymorphism of β-defensin-1 is associated with susceptibility to periodontitis in Japanese. Odontology. 2015 Jan;103(1):66-74.
Sarkisyan NG, Gankovskaya LV, Tuzankina IA, Svitich OA, Ron GI, Shershnev VN, et al. Association of polymorphic markers in genes of innate immunity in patients with periodontitis and inflammatory diseases of upper respiratory tract. Zh Mikrobiol Epidemiol Immunobiol. 2016;(1):67-71.
Zupin L, Robino A, Navarra CO, Pirastu N, Di Lenarda R, Gasparini P, et al. LTF and DEFB1 polymorphisms are associated with susceptibility toward chronic periodontitis development. Oral Dis. 2017;23(7):1001-08.
Soraia Aguiar de Melo Dias R, Carlos Mourão Pinho R, Almeida FR, Alfredo Farias Bandeira F, Celerino da Silva R, Crovella S, et al. Evaluation of DEFB1 polymorphisms in individuals with chronic periodontitis and diabetes mellitus type 2 in a population of northeastern Brazil. Spec Care Dentist. 2018;38(4):227-33.
Frandsen TF, Bruun Nielsen MF, Lindhardt CL, Eriksen MB. Using the full PICO model as a search tool for systematic reviews resulted in lower recall for some PICO elements. J Clin Epidemiol. 2020;127:69–75.
Epand RM, Vogel HJ. Diversity of antimicrobial peptides and their mechanisms of action. Biochimica et Biophysica Acta - Biomembranes. 1999;1462:11–28.
Gropp R, Frye M, Wagner TOF, Bargon J. Epithelial defensins impair adenoviral infection: implication for adenovirus-mediated gene therapy. Hum Gene Ther. 1999;10:957–964.
Harder J, Bartels J, Christophers E, Schröder JM. Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem. 2001;276:5707–5713.
Singh PK, Jia HP, Wiles K, Hesselberth J, Liu L, Conway BA, et al. Production of beta-defensins by human airway epithelia. Proc Natl Acad Sci U S A. 1998;95(25):14961-6.
Ganz T. Defensins: antimirobial peptipes of innate immunity. Nat Pub Gr. 2003;3:710–20.
Saitoh M, Abiko Y, Shimabukuro S, Kusano K, Nishimura M, Arakawa T, et al. Correlated expression of human beta defensin-1, -2 and -3 mRNAs in gingival tissues of young children. Arch Oral Biol. 2004;49(10):799-803.
Yang D, Liu ZH, Tewary P, Chen Q, de la Rosa G, Oppenheim JJ. Defensin participation in innate and adaptive immunity. Curr Pharm Des. 2007;13(30):3131-9.
Weinberg A, Jin G, Sieg S, McCormick TS. The yin and yang of human Beta-defensins in health and disease. Front Immunol. 2012;3:294.
Polesello V, Zupin L, Di Lenarda R, Biasotto M, Ottaviani G, Gobbo M, et al. Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration. Arch Oral Biol. 2015;60(7):1054-8.
Weinberg A, Krisanaprakornkit S, Dale BA. Epithelial antimicrobial peptides: Review and significance for oral applications. Crit Rev Oral Biol Med. 1998;9:399–414.
Dommisch H, Jepsen S. Diverse functions of defensins and other antimicrobial peptides in periodontal tissues. Periodontol 2000. 2015;69:96–110.
Kohlgraf KG, Pingel LC, Dietrich DE, Brogden KA. Defensins as anti-inflammatory compounds and mucosal adjuvants. Future Microbiol. 2010;5:99–113.
Diamond G, Kaiser V, Rhodes J, Russell JP, Bevins CL. Transcriptional regulation of β-defensin gene expression in tracheal epithelial cells. Infect Immun. 2000;68:113–19.
Ostaff MJ, Stange EF, Wehkamp J. Antimicrobial peptides and gut microbiota in homeostasis and pathology. EMBO Mol Med. 2013;5:1465–83.
Diamond G, Beckloff N, Weinberg A, Kisich K. The roles of antimicrobial peptides in innate host defense. Curr Pharm Design. 2009;15:(2009).
Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, et al. Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1. Nature. 2011;469(7330):419-23.
Jaeger SU, Schroeder BO, Meyer-Hoffert U, Courth L, Fehr SN, Gersemann M. Cell-mediated reduction of human β-defensin 1: A major role for mucosal thioredoxin. Mucosal Immunol. 2013;6:1179–90.
Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T. Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest. 1998;101(8):1633-42.
Townes CL, Ali A, Robson W, Pickard R, Hall J. Tolerance of bacteriuria after urinary diversion is linked to antimicrobial peptide activity. Urology. 2011 Feb;77(2):509.e1-8.
Becknell B, Spencer JD, Carpenter AR, Chen X, Singh A, Ploeger S, et al. Expression and antimicrobial function of beta-defensin 1 in the lower urinary tract. PLoS One. 2013;8(10):e77714.
Hiratsuka T, Nakazato M, Ihi T, Minematsu T, Chino N, Nakanishi T, et al. Structural analysis of human beta-defensin-1 and its significance in urinary tract infection. Nephron. 2000;85(1):34-40.
Hugo B. Dispensing by private practitioners [7]. South African Med J. 2002;92:666.
Bissell J, Joly S, Johnson GK, Organ CC, Dawson D, McCray PB Jr, et al. Expression of beta-defensins in gingival health and in periodontal disease. J Oral Pathol Med. 2004;33(5):278-85.
Tian Y, Li JL, Hao L, Yue Y, Wang M, Loo WT, et al. Association of cytokines, high sensitive C-reactive protein, VEGF and beta-defensin-1 gene polymorphisms and their protein expressions with chronic periodontitis in the Chinese population. Int J Biol Markers. 2013;28(1):100-7.
Sulijaya B, Tadjoedin FM, Kuswandani SO, Masulili SLC, Auerkari EI. Existence of human beta defensin-1 peptide on periodontal disease: an updated review based on case-control and cross-sectional studies. Asian J Appl Sci. 2017;10:50–56.
Taguchi Y, Imai H. Expression of beta-defensin-2 in human gingival epithelial cells in response to challenge with Porphyromonas gingivalis in vitro. J Periodontal Res. 2006;41(4):334-9.
Yamada M, Takahashi N, Matsuda Y, Sato K, Yokoji M, Sulijaya B, et al. A bacterial metabolite ameliorates periodontal pathogen-induced gingival epithelial barrier disruption via GPR40 signaling. Sci Rep. 2018;8:9008.
Bedi T, Mahendra J, Ambalavanan N. Defensins in periodontal health. Indian J Dent Res. 2015;26(4):340-4.
Nizet V. Antimicrobial peptide resistance mechanisms of human bacterial pathogens. Curr Issues Mol Biol. 2006;8(1):11-26.
Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol. 2005;3(3):238-50.
Prado-Montes de Oca E. Human beta-defensin 1: a restless warrior against allergies, infections and cancer. Int J Biochem Cell Biol. 2010;42(6):800-4.
Wohlfahrt JC, Wu T, Hodges JS, Hinrichs JE, Michalowicz BS. No association between selected candidate gene polymorphisms and severe chronic periodontitis. J Periodontol. 2006;77(3):426-36.
Milanese M, Segat L, Crovella S. Transcriptional effect of DEFB1 gene 5' untranslated region polymorphisms. Cancer Res. 2007;67(12):5997.
Nurjadi D, Herrmann E, Hinderberger I, Zanger P. Impaired β-defensin expression in human skin links DEFB1 promoter polymorphisms with persistent Staphylococcus aureus nasal carriage. J Infect Dis. 2013;207(4):666-74.
Boniotto M, Hazbón MH, Jordan WJ, Lennon GP, Eskdale J, Alland D, Gallagher G. Novel hairpin-shaped primer assay to study the association of the -44 single-nucleotide polymorphism of the DEFB1 gene with early-onset periodontal disease. Clin Diagn Lab Immunol. 2004;11(4):766-9.
Prado-Montes de Oca E, Velarde-Félix JS, Ríos-Tostado JJ, Picos-Cárdenas VJ, Figuera LE. SNP 668C (-44) alters a NF-kappaB1 putative binding site in non-coding strand of human beta-defensin 1 (DEFB1) and is associated with lepromatous leprosy. Infect Genet Evol. 2009;9(4):617-25.
Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA. Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol. 2003;41(1):90-6.
Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Clin Periodontol. 2018;45 Suppl 20:S149-S161
How to Cite
SULIJAYA, Benso; MASULILI, Sri Lelyati C; AUERKARI, Elza Ibrahim. Human Beta-defensin-1 and Periodontal Disease: The Past, Present, and Future. Journal of Indonesian Dental Association, [S.l.], v. 4, n. 1, p. 61-68, apr. 2021. ISSN 2621-6175. Available at: <>. Date accessed: 17 sep. 2021. doi:
Review Article