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International Journal of Dentistry
Volume 2012 (2012), Article ID 821383, 14 pages
http://dx.doi.org/10.1155/2012/821383
Review Article

Host-Bacteria Crosstalk at the Dentogingival Junction

1Department of Periodontology, Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, 20520 Turku, Finland
2Department of Cariology, Institute of Dentistry, University of Turku, Lemminkäisenkatu 2, 20520 Turku, Finland
3Department of Biochemistry and Food Chemistry, University of Turku, 20520 Turku, Finland
4Department of Periodontology, Institute of Dentistry, University of Helsinki, 00014 Helsinki, Finland
5Department of Oral and Maxillofacial Surgery, Helsinki University Central Hospital, 00290 Helsinki, Finland

Received 10 April 2012; Revised 22 May 2012; Accepted 22 May 2012

Academic Editor: Edvaldo Antonio Ribeiro Rosa

Copyright © 2012 M. T. Pöllänen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. D. Haffajee and S. S. Socransky, “Microbial etiological agents of destructive periodontal diseases,” Periodontology 2000, vol. 5, pp. 78–111, 1994. View at Scopus
  2. R. J. Genco, “Consensus report on periodontal diseases: pathogenesis and microbial factors,” in Annals of Periodontology, R. J. Genco, Ed., pp. 926–932, American Academy of Periodontology, Chicago, Ill, USA, 1996.
  3. S. S. Socransky and A. D. Haffajee, “Periodontal microbial ecology,” Periodontology 2000, vol. 38, pp. 135–187, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. P. S. Kumar, A. L. Griffen, M. L. Moeschberger, and E. J. Leys, “Identification of candidate periodontal pathogens and beneficial species by quantitative 16S clonal analysis,” Journal of Clinical Microbiology, vol. 43, no. 8, pp. 3944–3955, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. B. Zinsli Fritschi, A. Albert-Kiszely, and G. R. Persson, “Staphylococcus aureus and other bacteria in untreated periodontitis,” Journal of Dental Research, vol. 87, no. 6, pp. 589–593, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. A. P. V. Colombo, S. K. Boches, S. L. Cotton et al., “Comparisons of subgingival microbial profiles of refractory periodontitis, severe periodontitis, and periodontal health using the human oral microbe identification microarray,” Journal of Periodontology, vol. 80, no. 9, pp. 1421–1432, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Järvensivu, J. Hietanen, R. Rautemaa, T. Sorsa, and M. Richardson, “Candida yeasts in chronic periodontitis tissues and subgingival microbial biofilms in vivo,” Oral Diseases, vol. 10, no. 2, pp. 106–112, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. X. Song, E. R. K. Eribe, J. Sun, B. F. Hansen, and I. Olsen, “Genetic relatedness of oral yeasts within and between patients with marginal periodontitis and subjects with oral health,” Journal of Periodontal Research, vol. 40, no. 6, pp. 446–452, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. A. D. Haffajee and S. S. Socransky, “Microbiology of periodontal diseases: introduction,” Periodontology 2000, vol. 38, pp. 9–12, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Slots, “Herpesviruses in periodontal diseases,” Periodontology 2000, vol. 38, pp. 33–62, 2005. View at Publisher · View at Google Scholar · View at Scopus
  11. A. E. Duran-Pinedo, B. Paster, R. Teles, and J. Frias-Lopez, “Correlation network analysis applied to complex biofilm communities,” PLoS ONE, vol. 6, no. 12, Article ID e28438, 2011. View at Publisher · View at Google Scholar
  12. J. Frias-Lopez and A. Duran-Pinedo, “Effect of periodontal pathogens on the metatranscriptome of a healthy multispecies biofilm model,” Journal of Bacteriology, vol. 194, no. 8, pp. 2082–2095, 2012. View at Publisher · View at Google Scholar
  13. V. Cogoni, A. Morgan-Smith, J. Christopher Fenno, H. F. Jenkinson, and D. Dymock, “Treponema denticola chymotrypsin-like proteinase (CTLP) integrates spirochaetes within oral microbial communities,” Microbiology, vol. 158, no. 3, pp. 759–770, 2012. View at Publisher · View at Google Scholar
  14. A. W. Aruni, F. Roy, and H. M. Fletcher, “Filifactor alocis has virulence attributes that can enhance its persistence under oxidative stress conditions and mediate invasion of epithelial cells by Porphyromonas gingivalis,” Infection and Immunity, vol. 79, no. 10, pp. 3872–3886, 2011. View at Publisher · View at Google Scholar
  15. H. Shao and D. R. Demuth, “Quorum sensing regulation of biofilm growth and gene expression by oral bacteria and periodontal pathogens,” Periodontology 2000, vol. 52, no. 1, pp. 53–67, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. G. Hajishengallis, S. Liang, M. A. Payne et al., “Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement,” Cell Host and Microbe, vol. 10, no. 5, pp. 497–506, 2011. View at Publisher · View at Google Scholar
  17. J. I. Salonen, “Proliferative potential of the attached cells of human junctional epithelium,” Journal of Periodontal Research, vol. 29, no. 1, pp. 41–45, 1994. View at Scopus
  18. J. Oksanen, L. M. Sorokin, I. Virtanen, and M. Hormia, “The junctional epithelium around murine teeth differs from gingival epithelium in its basement membrane composition,” Journal of Dental Research, vol. 80, no. 12, pp. 2093–2097, 2001. View at Scopus
  19. M. Bickel, “The role of interleukin-8 in inflammation and mechanisms of regulation,” Journal of Periodontology, vol. 64, no. 5, pp. 456–460, 1993. View at Scopus
  20. J. M. Crawford, “Distribution of ICAM-1, LFA-3 and HLA-DR in healthy and diseased gingival tissues,” Journal of Periodontal Research, vol. 27, no. 4, pp. 291–298, 1992. View at Scopus
  21. N. Mukaida, A. Harada, K. Yasumoto, and K. Matsushima, “Properties of pro-inflammatory cell types-specific leukocyte chemotactic cytokinetis, interleukin 8(IL-8) and monocyte chemotactic and activating factor (MCAF),” Microbiology and Immunology, vol. 36, no. 8, pp. 773–789, 1992. View at Scopus
  22. M. S. Tonetti, M. A. Imboden, L. Gerber, N. P. Lang, J. Laissue, and C. Mueller, “Localized expression of mRNA for phagocyte-specific chemotactic cytokines in human periodontal infections,” Infection and Immunity, vol. 62, no. 9, pp. 4005–4014, 1994. View at Scopus
  23. B. A. Dale, “Periodontal epithelium: a newly recognized role in health and disease,” Periodontology 2000, vol. 30, no. 1, pp. 70–78, 2002. View at Scopus
  24. M. Miyauchi, S. Sato, S. Kitagawa et al., “Cytokine expression in rat molar gingival periodontal tissues after topical application of lipopolysaccharide,” Histochemistry and Cell Biology, vol. 116, no. 1, pp. 57–62, 2001. View at Scopus
  25. K. F. Ross and M. C. Herzberg, “Calprotectin expression by gingival epithelial cells,” Infection and Immunity, vol. 69, no. 5, pp. 3248–3254, 2001. View at Publisher · View at Google Scholar · View at Scopus
  26. D. L. Diamond, J. R. Kimball, S. Krisanaprakornkit, T. Ganz, and B. A. Dale, “Detection of β-defensins secreted by human oral epithelial cells,” Journal of Immunological Methods, vol. 256, no. 1-2, pp. 65–76, 2001. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Mathews, H. P. Jia, J. M. Guthmiller et al., “Production of β-defensin antimicrobial peptides by the oral mucosa and salivary glands,” Infection and Immunity, vol. 67, no. 6, pp. 2740–2745, 1999. View at Scopus
  28. Q. Lu, L. Jin, R. P. Darveau, and L. P. Samaranayake, “Expression of human β-defensins-1 and -2 peptides in unresolved chronic periodontitis,” Journal of Periodontal Research, vol. 39, no. 4, pp. 221–227, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Noguchi, H. Shiba, H. Komatsuzawa et al., “Syntheses of prostaglandin E2 and E-cadherin and gene expression of β-defensin-2 by human gingival epithelial cells in response to actinobacillus actinomycetemcomitans,” Inflammation, vol. 27, no. 6, pp. 341–349, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. A. Vankeerberghen, H. Nuytten, K. Dierickx, M. Quirynen, J. J. Cassiman, and H. Cuppens, “Differential induction of human beta-defensin expression by periodontal commensals and pathogens in periodontal pocket epithelial cells,” Journal of Periodontology, vol. 76, no. 8, pp. 1293–1303, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. W. O. Chung, S. R. Hansen, D. Rao, and B. A. Dale, “Protease-activated receptor signaling increases epithelial antimicrobial peptide expression,” Journal of Immunology, vol. 173, no. 8, pp. 5165–5170, 2004. View at Scopus
  32. K. Nisapakultorn, K. F. Ross, and M. C. Herzberg, “Calprotectin expression in vitro by oral epithelial cells confers resistance to infection by Porphyromonas gingivalis,” Infection and Immunity, vol. 69, no. 7, pp. 4242–4247, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. U. K. Gursoy, E. Könönen, N. Luukkonen, and V. J. Uitto, “Human neutrophil defensins and their effect on epithelial cells,” Journal of Periodontology. In press.
  34. V. J. Uitto, J. I. Salonen, J. D. Firth, H. Jousimies-Somer, and U. Saarialho-Kere, “Matrilysin (matrix metalloproteinase-7) expression in human junctional epithelium,” Journal of Dental Research, vol. 81, no. 4, pp. 241–246, 2002. View at Scopus
  35. C. L. Wilson, A. J. Ouellette, D. P. Satchell et al., “Regulation of intestinal α-defensin activation by the metalloproteinase matrilysin in innate host defense,” Science, vol. 286, no. 5437, pp. 113–117, 1999. View at Publisher · View at Google Scholar · View at Scopus
  36. Y. S. López-Boado, C. L. Wilson, L. V. Hooper, J. I. Gordon, S. J. Hultgren, and W. C. Parks, “Bacterial exposure induces and activates matrilysin in mucosal epithelial cells,” Journal of Cell Biology, vol. 148, no. 6, pp. 1305–1315, 2000. View at Publisher · View at Google Scholar · View at Scopus
  37. P. N. Madianos, Y. A. Bobetsis, and D. F. Kinane, “Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva,” Journal of Clinical Periodontology, vol. 32, no. 6, pp. 57–71, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. T. Njoroge, R. J. Genco, H. T. Sojar, N. Hamada, and C. A. Genco, “A role for fimbriae in Porphyromonas gingivalis invasion of oral epithelial cells,” Infection and Immunity, vol. 65, no. 5, pp. 1980–1984, 1997. View at Scopus
  39. H. Loppnow, H. Brade, E. T. Rietschel, and H. D. Flad, “Induction of cytokines in mononuclear and vascular cells by endotoxin and other bacterial products,” Methods in Enzymology, vol. 236, pp. 3–10, 1994. View at Publisher · View at Google Scholar · View at Scopus
  40. K. Monefeldt and T. Tollefsen, “Effects of a streptococcal lipoteichoic acid on complement activation in vitro,” Journal of Clinical Periodontology, vol. 20, no. 3, pp. 186–192, 1993. View at Scopus
  41. S. Bhakdi, T. Klonisch, P. Nuber, and W. Fischer, “Stimulation of monokine production by lipoteichoic acids,” Infection and Immunity, vol. 59, no. 12, pp. 4614–4620, 1991. View at Scopus
  42. E. H. Beachey and W. A. Simpson, “The adherence of group A streptococci to oropharyngeal cells: the lipoteichoic acid adhesin and fibronectin receptor,” Infection, vol. 10, no. 2, pp. 107–111, 1982. View at Scopus
  43. S. C. Holt and T. E. Bramanti, “Factors in virulence expression and their role in periodontal disease pathogenesis,” Critical Reviews in Oral Biology and Medicine, vol. 2, no. 2, pp. 177–281, 1991. View at Scopus
  44. G. Rölla, O. J. Iversen, and P. Bonesvoll, “Lipoteichoic acid—the key to the adhesiveness of sucrose grown Streptococcus mutans,” Advances in Experimental Medicine and Biology, vol. 107, pp. 607–617, 1978. View at Scopus
  45. M. T. Pöllänen, J. I. Salonen, D. Grenier, and V. J. Uitto, “Epithelial cell response to challenge of bacterial lipoteichoic acids and lipopolysaccharides in vitro,” Journal of Medical Microbiology, vol. 49, no. 3, pp. 245–252, 2000. View at Scopus
  46. I. A. Bab, M. N. Sela, I. Ginsburg, and T. Dishon, “Inflammatory lesions and bone resorption induced in the rat periodontium by lipoteichoic acid of Streptococcus mutans,” Inflammation, vol. 3, no. 4, pp. 345–358, 1979. View at Scopus
  47. E. Hausmann, B. C. Nair, and R. Dziak, “Bacterial components which result in bone loss,” in Hos Parasite Interactions in Periodontal Diseases, R. J. Genco and S. E. Merhagen, Eds., pp. 151–159, American Society for Microbiology, Washington, DC, USA, 1982.
  48. D. N. Tatakis and P. S. Kumar, “Etiology and pathogenesis of periodontal diseases,” Dental Clinics of North America, vol. 49, no. 3, pp. 491–516, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. A. L. Salzman, W. Hailong, P. S. Wollert et al., “Endotoxin-induced ileal mucosal hyperpermeability in pigs: role of tissue acidosis,” American Journal of Physiology, vol. 266, no. 4, pp. G633–G646, 1994. View at Scopus
  50. R. Snyderman, “Role for endotoxin and complement in periodontal tissue destruction,” Journal of Dental Research, vol. 51, no. 2, pp. 356–361, 1972. View at Scopus
  51. P. M. Bartold, A. S. Narayanan, and R. C. Page, “Platelet-derived growth factor reduces the inhibitory effects of lipopolysaccharide on gingival fibroblast proliferation,” Journal of Periodontal Research, vol. 27, no. 5, pp. 499–505, 1992. View at Scopus
  52. F. A. DeRenzis and S. Y. Chen, “Ultrastructural study of cultured human gingival fibroblasts exposed to endotoxin,” Journal of Periodontology, vol. 54, no. 2, pp. 86–90, 1983. View at Scopus
  53. S. J. Hill and J. L. Ebersole, “The effect of lipopolysaccharide on growth factor-induced mitogenesis in human gingival fibroblasts,” Journal of Periodontology, vol. 67, no. 12, pp. 1274–1280, 1996. View at Scopus
  54. S. Kamin, W. Harvey, M. Wilson, and A. Scutt, “Inhibition of fibroblast proliferation and collagen synthesis by capsular material from Actinobacillus actinomycetemcomitans,” Journal of Medical Microbiology, vol. 22, no. 3, pp. 245–249, 1986. View at Scopus
  55. H. Larjava, V. J. Uitto, E. Eerola, and M. Haapasalo, “Inhibition of gingival fibroblast growth by Bacteroides gingivalis,” Infection and Immunity, vol. 55, no. 1, pp. 201–205, 1987. View at Scopus
  56. D. L. Layman and D. L. Diedrich, “Growth inhibitory effects of endotoxins from Bacteroides gingivalis and intermedius on human gingival fibroblasts in vitro,” Journal of Periodontology, vol. 58, no. 6, pp. 387–392, 1987. View at Scopus
  57. T. Takata, M. Miyauchi, I. Ogawa, H. Ito, J. Kobayashi, and H. Nikai, “Reactive change in proliferative activity of the junctional epithelium after topical application of lipopolysaccharide,” Journal of Periodontology, vol. 68, no. 6, pp. 531–535, 1997. View at Scopus
  58. B. Zhang, B. Wang, Y. Chen, J. Yang, and J. Zhang, “Influence of lipopolysaccharide and interleukin-2 on proliferation and synthesis of sulfated macromolecules in cultured rat glomerular epithelial cells,” Chinese Medical Journal, vol. 109, no. 8, pp. 609–614, 1996. View at Scopus
  59. C. Eftimiadi, S. Valente, S. Mangiante, P. E. Mangiante, and R. Niederman, “Short chain fatty acids produced by anaerobic bacteria inhibit adhesion and proliferation of periodontal ligament fibroblasts,” Minerva Stomatologica, vol. 42, no. 11-12, pp. 481–485, 1993. View at Scopus
  60. M. T. Pöllänen, D. O. Overman, and J. I. Salonen, “Bacterial metabolites sodium butyrate and propionate inhibit epithelial cell growth in vitro,” Journal of Periodontal Research, vol. 32, no. 3, pp. 326–334, 1997. View at Scopus
  61. R. E. Singer and B. A. Buckner, “Butyrate and propionate: important components of toxic dental plaque extracts,” Infection and Immunity, vol. 32, no. 2, pp. 458–463, 1981. View at Scopus
  62. B. C. Sorkin and R. Niederman, “Short chain carboxylic acids decrease human gingival keratinocyte proliferation and increase apoptosis and necrosis,” Journal of Clinical Periodontology, vol. 25, no. 4, pp. 311–315, 1998. View at Scopus
  63. R. E. Singer and B. A. Buckner, “Propionate and butyrate induction of gingival inflammation in the beagle,” Journal of Dental Research, vol. 59, abstract, 670, 1980.
  64. S. Urnowey, T. Ansai, V. Bitko, K. Nakayama, T. Takehara, and S. Barik, “Temporal activation of anti- and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis: potential role of bacterial proteases in host signalling,” BMC Microbiology, vol. 6, article 26, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Paju, F. Goulhen, S. Asikainen, D. Grenier, D. Mayrand, and V. J. Uitto, “Localization of heat shock proteins in clinical Actinobacillus actinomycetemcomitans strains and their effects on epithelial cell proliferation,” FEMS Microbiology Letters, vol. 182, no. 2, pp. 231–235, 2000. View at Publisher · View at Google Scholar · View at Scopus
  66. G. N. Belibasakis, M. Brage, T. Lagergård, and A. Johansson, “Cytolethal distending toxin upregulates RANKL expression in Jurkat T-cells,” Acta Pathologica, Microbiologica et Immunologica, vol. 116, no. 6, pp. 499–506, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. T. J. van Steenbergen, L. M. van der Mispel, and J. de Graaff, “Effects of ammonia and volatile fatty acids produced by oral bacteria on tissue culture cells,” Journal of Dental Research, vol. 65, no. 6, pp. 909–912, 1986. View at Scopus
  68. K. Helgeland, “Inhibitory effect of NH4Cl on secretion of collagen in human gingival fibroblasts,” Scandinavian Journal of Dental Research, vol. 92, no. 5, pp. 419–425, 1984. View at Scopus
  69. O. M. Carro, S. A. S. Evans, and C. W. Leone, “Effect of inflammation on the proliferation of human gingival epithelial cells in vitro,” Journal of Periodontology, vol. 68, no. 11, pp. 1070–1075, 1997. View at Scopus
  70. L. Vitkov, W. D. Krautgartner, and M. Hannig, “Bacterial internalization in periodontitis,” Oral Microbiology and Immunology, vol. 20, no. 5, pp. 317–321, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. E. Andrian, D. Grenier, and M. Rouabhia, “In vitro models of tissue penetration and destruction by Porphyromonas gingivalis,” Infection and Immunity, vol. 72, no. 8, pp. 4689–4698, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. D. Ekuni, T. Tomofuji, R. Yamanaka, K. Tachibana, T. Yamamoto, and T. Watanabe, “Initial apical migration of junctional epithelium in rats following application of lipopolysaccharide and proteases,” Journal of Periodontology, vol. 76, no. 1, pp. 43–48, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. L. Ren, W. K. Leung, R. P. Darveau, and L. Jin, “The expression profile of lipopolysaccharide-binding protein, membrane-bound CD14, and toll-like receptors 2 and 4 in chronic periodontitis,” Journal of Periodontology, vol. 76, no. 11, pp. 1950–1959, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. A. Uehara, K. Muramoto, H. Takada, and S. Sugawara, “Neutrophil serine proteinases activate human nonepithelial cells to produce inflammatory cytokines through protease-activated receptor 2,” Journal of Immunology, vol. 170, pp. 5690–5696, 2003.
  75. L. A. Abraham, C. Chinni, A. L. Jenkins et al., “Expression of protease-activated receptor-2 by osteoblasts,” Bone, vol. 26, no. 1, pp. 7–14, 2000. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Lourbakos, J. Potempa, J. Travis et al., “Arginine-specific protease from Porphyromonas gingivalis activates protease-activated receptors on human oral epithelial cells and induces interleukin-6 secretion,” Infection and Immunity, vol. 69, no. 8, pp. 5121–5130, 2001. View at Publisher · View at Google Scholar · View at Scopus
  77. R. P. Darveau, C. M. Belton, R. A. Reife, and R. J. Lamont, “Local chemokine paralysis, a novel pathogenic mechanism for porphyromonas gingivalis,” Infection and Immunity, vol. 66, no. 4, pp. 1660–1665, 1998. View at Scopus
  78. G. T. J. Huang, D. Kim, J. K. H. Lee, H. K. Kuramitsu, and S. Kinder, “Interleukin-8 and intercellular adhesion molecule 1 regulation in oral epithelial cells by selected periodontal bacteria: multiple effects of Porphyromonas gingivalis via antagonistic mechanisms,” Infection and Immunity, vol. 69, no. 3, pp. 1364–1372, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. M. Holzhausen, L. C. Spolidorio, and N. Vergnolle, “Proteinase-activated receptor-2 (PAR2) agonist causes periodontitis in rats,” Journal of Dental Research, vol. 84, no. 2, pp. 154–159, 2005. View at Publisher · View at Google Scholar · View at Scopus
  80. J. J. Reynolds, “Collagenases and tissue inhibitors of metalloproteinases: a functional balance in tissue degradation,” Oral Diseases, vol. 2, no. 1, pp. 70–76, 1996. View at Scopus
  81. L. Hakkinen, J. Heino, L. Kiovisto, and H. Larjava, “Altered interaction of human granulation-tissue fibroblasts with fibronectin is regulated α5β1 integrin,” Biochimica et Biophysica Acta, vol. 1224, no. 1, pp. 33–42, 1994. View at Publisher · View at Google Scholar · View at Scopus
  82. L. Häkkinen and H. Larjava, “Characterization of fibroblast clones from periodontal granulation tissue in vitro,” Journal of Dental Research, vol. 71, no. 12, pp. 1901–1907, 1992. View at Scopus
  83. R. C. Page and H. E. Schroeder, “Pathogenesis of inflammatory periodontal disease: a summary of current work,” Laboratory Investigation, vol. 34, no. 3, pp. 235–249, 1976. View at Scopus
  84. D. F. Kinane and J. Lindhe, “Pathogenesis of periodontitis,” in Clinical Periodontology and Implant dentistry, J. Lindhe, T. Karring, and N. P. lang, Eds., pp. 189–225, Munksgaard, Copenhagen, Denmark, 1997.
  85. A. Beklen, M. Ainola, M. Hukkanen, C. Gürgan, T. Sorsa, and Y. T. Konttinen, “MMPs, IL-1, and TNF are regulated by IL-17 in periodontitis,” Journal of Dental Research, vol. 86, no. 4, pp. 347–351, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. H. Domeij, T. Modéer, and T. Yucel-Lindberg, “Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 production in human gingival fibroblasts: the role of protein kinase C,” Journal of Periodontal Research, vol. 39, no. 5, pp. 308–314, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. J. J. Reynolds and M. C. Meikle, “Mechanisms of connective tissue matrix destruction in periodontitis,” Periodontology 2000, vol. 1997, no. 14, pp. 144–157, 1997. View at Scopus
  88. Z. Feng and A. Weinberg, “Role of bacteria in health and disease of periodontal tissues,” Periodontology 2000, vol. 40, no. 1, pp. 50–76, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. J. Carlsson, B. F. Herrmann, J. F. Hofling, and G. K. Sundqvist, “Degradation of the human proteinase inhibitors alpha-1-antitrypsin and alpha-2-macroglobulin by Bacteroides gingivalis,” Infection and Immunity, vol. 43, no. 2, pp. 644–648, 1984. View at Scopus
  90. L. Sandholm, “Proteases and their inhibitors in chronic inflammatory periodontal disease,” Journal of Clinical Periodontology, vol. 13, no. 1, pp. 19–26, 1986. View at Scopus
  91. T. Nilsson, J. Carlsson, and G. Sundqvist, “Inactivation of key factors of the plasma proteinase cascade systems by Bacteroides gingivalis,” Infection and Immunity, vol. 50, no. 2, pp. 467–471, 1985. View at Scopus
  92. D. Nelson, J. Potempa, T. Kordula, and J. Travis, “Purification and characterization of a novel cysteine proteinase (periodontain) from Porphyromonas gingivalis: evidence for a role in the inactivation of human α1-proteinase inhibitor,” Journal of Biological Chemistry, vol. 274, no. 18, pp. 12245–12251, 1999. View at Publisher · View at Google Scholar · View at Scopus
  93. H. Birkedal-Hansen, “Role of cytokines and inflammatory mediators in tissue destruction,” Journal of Periodontal Research, vol. 28, no. 6, pp. 500–510, 1993. View at Scopus
  94. T. Kubota, T. Nomura, T. Takahashi, and K. Hara, “Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in periodontitis-affected human gingival tissue,” Archives of Oral Biology, vol. 41, no. 3, pp. 253–262, 1996. View at Scopus
  95. Y. T. Teng, J. Sodek, and C. A. McCulloch, “Gingival crevicular fluid gelatinase and its relationship to periodontal disease in human subjects,” Journal of Periodontal Research, vol. 27, no. 5, pp. 544–552, 1992. View at Scopus
  96. M. Soell, R. Elkaim, and H. Tenenbaum, “Cathepsin C, matrix metalloproteinases, and their tissue inhibitors in gingiva and gingival crevicular fluid from periodontitis-affected patients,” Journal of Dental Research, vol. 81, no. 3, pp. 174–178, 2002. View at Scopus
  97. T. Sorsa, L. Tjäderhane, and T. Salo, “Matrix metalloproteinases (MMPs) in oral diseases,” Oral Diseases, vol. 10, no. 6, pp. 311–318, 2004. View at Publisher · View at Google Scholar · View at Scopus
  98. M. Hernandez, M. A. Valenzuela, C. Lopez-Otin et al., “Matrix metalloproteinase-13 is highly expressed in destructive periodontal disease activity,” Journal of Periodontology, vol. 77, no. 11, pp. 1863–1870, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Mäkelä, T. Salo, V. J. Uitto, and H. Larjava, “Matrix metalloproteinases (MMP-2 and MMP-9) of the oral cavity: cellular origin and relationship to periodontal status,” Journal of Dental Research, vol. 73, no. 8, pp. 1397–1406, 1994. View at Scopus
  100. V. J. Uitto, C. M. Overall, and C. McCulloch, “Proteolytic host cell enzymes in gingival crevice fluid,” Periodontology 2000, vol. 31, pp. 77–104, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. P. Pozo, M. A. Valenzuela, C. Melej et al., “Longitudinal analysis of metalloproteinases, tissue inhibitors of metalloproteinases and clinical parameters in gingival crevicular fluid from periodontitis-affected patients,” Journal of Periodontal Research, vol. 40, no. 3, pp. 199–207, 2005. View at Publisher · View at Google Scholar · View at Scopus
  102. M. Lorencini, J. A. F. Silva, C. A. Almeida, A. Bruni-Cardoso, H. F. Carvalho, and D. R. Stach-Machado, “A new paradigm in the periodontal disease progression: gingival connective tissue remodeling with simultaneous collagen degradation and fibers thickening,” Tissue and Cell, vol. 41, no. 1, pp. 43–50, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. R. Attström, “Studies on neutrophil polymorphonuclear leukocytes at the dento-gingival junction in gingival health and disease,” Journal of Periodontal Research, vol. 8, supplement, pp. 1–15, 1971. View at Scopus
  104. P. R. Garant, “Plaque: neutrophil interaction in monoinfected rats as visualized by transmission electron microscopy,” Journal of Periodontology, vol. 47, no. 3, pp. 132–138, 1976. View at Scopus
  105. J. B. Matthews, H. J. Wright, A. Roberts, N. Ling-Mountford, P. R. Cooper, and I. L. C. Chapple, “Neutrophil hyper-responsiveness in periodontitis,” Journal of Dental Research, vol. 86, no. 8, pp. 718–722, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. T. Sorsa, K. Suomalainen, and V. J. Uitto, “The role of gingival crevicular fluid and salivary interstitial collagenases in human periodontal diseases,” Archives of Oral Biology, vol. 35, no. 1, pp. S193–S196, 1990. View at Publisher · View at Google Scholar · View at Scopus
  107. P. Visca, F. Berlutti, P. Vittorioso, C. Dalmastri, M. C. Thaller, and P. Valenti, “Growth and adsorption of Streptococcus mutans 6715-13 to hydroxyapatite in the presence of lactoferrin,” Medical Microbiology and Immunology, vol. 178, no. 2, pp. 69–79, 1989. View at Scopus
  108. R. M. Wilson and W. G. Reeves, “Neutrophil phagocytosis and killing in insulin-dependent diabetes,” Clinical and Experimental Immunology, vol. 63, no. 2, pp. 478–484, 1986.
  109. L. C. Altman, C. Baker, P. Fleckman, D. Luchtel, and D. Oda, “Neutrophil-mediated damage to human gingival epithelial cells,” Journal of Periodontal Research, vol. 27, no. 1, pp. 70–79, 1992. View at Scopus
  110. D. K. Dennison and T. E. Van Dyke, “The acute inflammatory response and the role of phagocytic cells in periodontal health and disease,” Periodontology 2000, vol. 1997, no. 14, pp. 54–78, 1997. View at Scopus
  111. J. Carlsson, “Growth and nutrition as ecological factors,” in Oral Bacterial Ecology: The Molecular Basis, H. Kuramitsu and R. Ellen, Eds., pp. 67–130, Horizon Scientific Press, Norfolk, Va, USA, 2000.
  112. M. T. Pöllänen, J. I. Salonen, and V. J. Uitto, “Structure and function of the tooth-epithelial interface in health and disease,” Periodontology 2000, vol. 31, pp. 12–31, 2003. View at Publisher · View at Google Scholar · View at Scopus
  113. L. M. Golub, H. M. Lee, R. A. Greenwald et al., “A matrix metalloproteinase inhibitor reduces bone-type collagen degradation fragments and specific collagenases in gingival crevicular fluid during adult periodontitis,” Inflammation Research, vol. 46, no. 8, pp. 310–319, 1997. View at Publisher · View at Google Scholar · View at Scopus
  114. P. Permpanich, M. J. Kowolik, and D. M. Galli, “Resistance of fluorescent-labelled Actinobacillus actinomycetemcomitans strains to phagocytosis and killing by human neutrophils,” Cellular Microbiology, vol. 8, no. 1, pp. 72–84, 2006. View at Publisher · View at Google Scholar · View at Scopus
  115. R. K. Liu, C. F. Cao, H. X. Meng, and Y. Gao, “Polymorphonuclear neutrophils and their mediators in gingival tissues from generalized aggressive periodontitis,” Journal of Periodontology, vol. 72, no. 11, pp. 1545–1553, 2001. View at Publisher · View at Google Scholar · View at Scopus
  116. A. Güntsch, M. Erler, P. M. Preshaw, B. W. Sigusch, G. Klinger, and E. Glockmann, “Effect of smoking on crevicular polymorphonuclear neutrophil function in periodontally healthy subjects,” Journal of Periodontal Research, vol. 41, no. 3, pp. 184–188, 2006. View at Publisher · View at Google Scholar · View at Scopus
  117. A. Gustafsson, H. Ito, B. Åsman, and K. Bergström, “Hyper-reactive mononuclear cells and neutrophils in chronic periodontitis,” Journal of Clinical Periodontology, vol. 33, no. 2, pp. 126–129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. E. A. Nicu, U. Van Der Velden, V. Everts, A. J. Van Winkelhoff, D. Roos, and B. G. Loos, “Hyper-reactive PMNs in FcγRIIa 131 H/H genotype periodontitis patients,” Journal of Clinical Periodontology, vol. 34, no. 11, pp. 938–945, 2007. View at Publisher · View at Google Scholar · View at Scopus
  119. F. Ghannad, D. Nica, M. I. Garcia Fulle et al., “Absence of αvβ6 integrin is linked to initiation and progression of periodontal disease,” American Journal of Pathology, vol. 172, no. 5, pp. 1271–1286, 2008. View at Publisher · View at Google Scholar · View at Scopus
  120. G. Hajishengallis and J. D. Lambris, “Microbial manipulation of receptor crosstalk in innate immunity,” Nature Reviews Immunology, vol. 11, no. 3, pp. 187–200, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. H. Rus, C. Cudrici, and F. Niculescu, “The role of the complement system in innate immunity,” Immunologic Research, vol. 33, no. 2, pp. 103–112, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. R. Attstrom, A. B. Laurel, U. Lahsson, and A. Sjoholm, “Complement factors in gingival crevice material from healthy and inflamed gingiva in humans,” Journal of Periodontal Research, vol. 10, no. 1, pp. 19–27, 1975. View at Scopus
  123. H. A. Schenkein and R. J. Genco, “Gingival fluid and serum in periodontal diseases. I. Quantitative study of immunoglobulins, complement components, and other plasma proteins,” Journal of Periodontology, vol. 48, no. 2, pp. 772–777, 1977. View at Scopus
  124. H. A. Schenkein and R. J. Genco, “Gingival fluid and serum in periodontal diseases. II. Evidence for cleavage of complement components C3, C3 proactivator (factor B) and C4 in gingival fluid,” Journal of Periodontology, vol. 48, no. 2, pp. 778–784, 1977. View at Scopus
  125. K. Monefeldt, K. Helgeland, and T. Tollefsen, “In vitro cleavage of serum complement protein C3: a comparison between patients with adult periodontitis and periodontally healthy persons,” Journal of Clinical Periodontology, vol. 22, no. 1, pp. 45–51, 1995. View at Scopus
  126. J. A. Wingrove, R. G. DiScipio, Z. Chen, J. Potempa, J. Travis, and T. E. Hugli, “Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis,” Journal of Biological Chemistry, vol. 267, no. 26, pp. 18902–18907, 1992. View at Scopus
  127. T. Yamazaki, M. Miyamoto, S. Yamada, K. Okuda, and K. Ishihara, “Surface protease of Treponema denticola hydrolyzes C3 and influences function of polymorphonuclear leukocytes,” Microbes and Infection, vol. 8, no. 7, pp. 1758–1763, 2006. View at Publisher · View at Google Scholar · View at Scopus
  128. E. P. Næsse, O. Schreurs, K. Helgeland, K. Schenck, and S. Steinsvoll, “Matrix metalloproteinases and their inhibitors in gingival mast cells in persons with and without human immunodeficiency virus infection,” Journal of Periodontal Research, vol. 38, no. 6, pp. 575–582, 2003. View at Publisher · View at Google Scholar · View at Scopus
  129. M. R. Patters, C. E. Niekrash, and N. P. Lang, “Assessment of complement cleavage in gingival fluid during experimental gingivitis in man,” Journal of Clinical Periodontology, vol. 16, no. 1, pp. 33–37, 1989. View at Scopus
  130. R. Rautemaa and S. Meri, “Protection of gingival epithelium against complement-mediated damage by strong expression of the membrane attack complex inhibitor protectin (CD59),” Journal of Dental Research, vol. 75, no. 1, pp. 568–574, 1996. View at Scopus
  131. M. S. Tonetti, “Molecular factors associated with compartmentalization of gingival immune responses and transepithelial neutrophil migration,” Journal of Periodontal Research, vol. 32, no. 1, pp. 104–109, 1997. View at Scopus
  132. M. A. Jagels, J. A. Ember, J. Travis, J. Potempa, R. Pike, and T. E. Hugli, “Cleavage of the human C5a receptor by proteinases derived from porphyromonas gingivalis: cleavage of leukocyte C5a Receptor,” Advances in Experimental Medicine and Biology, vol. 389, pp. 155–164, 1996. View at Scopus
  133. N. Yamaguchi, H. Tsuda, Y. Yamashita, and T. Koga, “Binding of the capsule-like serotype-specific polysaccharide antigen and the lipopolysaccharide from Actinobacillus actinomycetemcomitans to human complement-derived opsonins,” Oral Microbiology and Immunology, vol. 13, no. 6, pp. 348–354, 1998. View at Scopus
  134. T. Imamura, J. Travis, and J. Potempa, “The biphasic virulence activities of gingipains: activation and inactivation of host proteins,” Current Protein and Peptide Science, vol. 4, no. 6, pp. 443–450, 2003. View at Publisher · View at Google Scholar · View at Scopus
  135. K. Popadiak, J. Potempa, K. Riesbeck, and A. M. Blom, “Biphasic effect of gingipains from Porphyromonas gingivalis on the human complement system,” Journal of Immunology, vol. 178, no. 11, pp. 7242–7250, 2007. View at Scopus
  136. M. Seppänen, M. L. Lokki, I. L. Notkola et al., “Complement and C4 null alleles in severe chronic adult periodontitis,” Scandinavian Journal of Immunology, vol. 65, no. 2, pp. 176–181, 2007. View at Publisher · View at Google Scholar · View at Scopus
  137. C. W. Cutler and Y. T. A. Teng, “Oral mucosal dendritic cells and periodontitis: many sides of the same coin with new twists,” Periodontology 2000, vol. 45, no. 1, pp. 35–50, 2007. View at Publisher · View at Google Scholar · View at Scopus
  138. K. S. Kornman, “The interleukin-1 genotype as a severity factor in adult periodontal disease,” Journal of Clinical Periodontology, vol. 24, no. 1, pp. 72–77, 1997.
  139. K. S. Kornman and F. S. di Giovine, “Genetic variations in cytokine expression: a risk factor for severity of adult periodontitis,” Annals of Periodontology, vol. 3, no. 1, pp. 327–338, 1998. View at Scopus
  140. T. C. Hart and K. S. Kornman, “Genetic factors in the pathogenesis of periodontitis,” Periodontology 2000, vol. 1997, no. 14, pp. 202–215, 1997. View at Scopus
  141. G. Greenstein and T. C. Hart, “Clinical utility of a genetic susceptibility test for severe chronic periodontitis: a critical evaluation,” Journal of the American Dental Association, vol. 133, no. 4, pp. 452–459, 2002. View at Scopus
  142. G. Greenstein and T. C. Hart, “A critical assessment of interleukin-1 (IL-1) genotyping when used in a genetic susceptibility test for severe chronic periodontitis,” Journal of Periodontology, vol. 73, no. 2, pp. 231–247, 2002. View at Publisher · View at Google Scholar · View at Scopus
  143. Y. T. A. Teng, “Protective and destructive immunity in the periodontium—part 1—innate and humoral immunity and the periodontium,” Journal of Dental Research, vol. 85, no. 3, pp. 198–208, 2006. View at Publisher · View at Google Scholar · View at Scopus
  144. P. Kidd, “Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease,” Alternative Medicine Review, vol. 8, no. 3, pp. 223–246, 2003. View at Scopus
  145. D. F. Kinane and D. F. Lappin, “Immune processes in periodontal disease: a review,” Annals of Periodontology, vol. 7, no. 1, pp. 62–71, 2002. View at Scopus
  146. M. H. Napimoga, L. H. A. C. Nunes, A. A. B. Maciel et al., “Possible Involvement of IL-21 and IL-10 on Salivary IgA Levels in Chronic Periodontitis Subjects,” Scandinavian Journal of Immunology, vol. 74, no. 6, pp. 596–602, 2011. View at Publisher · View at Google Scholar
  147. P. J. Pussinen, E. Könönen, S. Paju et al., “Periodontal pathogen carriage, rather than periodontitis, determines the serum antibody levels,” Journal of Clinical Periodontology, vol. 38, no. 5, pp. 405–411, 2011. View at Publisher · View at Google Scholar · View at Scopus
  148. E. Gemmell, K. Yamazaki, and G. J. Seymour, “Destructive periodontitis lesions are determined by the nature of the lymphocytic response,” Critical Reviews in Oral Biology and Medicine, vol. 13, no. 1, pp. 17–34, 2002. View at Scopus
  149. K. Yamazaki, H. Yoshie, and G. J. Seymour, “T cell regulation of the immune response to infection in periodontal diseases,” Histology and Histopathology, vol. 18, no. 3, pp. 889–896, 2003. View at Scopus
  150. M. A. Taubman, P. Valverde, X. Han, and T. Kawai, “Immune response: they key to bone resorption in periodontal disease,” Journal of Periodontology, vol. 76, no. 11, pp. 2033–2041, 2005. View at Publisher · View at Google Scholar · View at Scopus
  151. Y. T. A. Teng, “Protective and destructive immunity in the periodontium—part 2—T-cell-mediated immunity in the periodontium,” Journal of Dental Research, vol. 85, no. 3, pp. 209–219, 2006. View at Publisher · View at Google Scholar · View at Scopus
  152. Y. Choi, K. M. Woo, S.-H. Ko, Y. J. Lee, S.-J. Park, and H.-M. Kim, “Osteoclastogenesis is enhanced by activated B cells but suppressed by activated CD8+ T cells,” European Journal of Immunology, vol. 31, no. 7, pp. 2179–2188, 2001. View at Publisher · View at Google Scholar
  153. Y. Y. Kung, U. Felge, I. Sarosi et al., “Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand,” Nature, vol. 402, no. 6759, pp. 304–309, 1999. View at Publisher · View at Google Scholar · View at Scopus
  154. G. J. Seymour and E. Gemmell, “Cytokines in periodontal disease: where to from here?” Acta Odontologica Scandinavica, vol. 59, no. 3, pp. 167–173, 2001. View at Publisher · View at Google Scholar · View at Scopus
  155. D. L. Cochran, “Inflammation and bone loss in periodontal disease,” Journal of Periodontology, vol. 79, no. 8, pp. 1569–1576, 2008. View at Publisher · View at Google Scholar · View at Scopus
  156. N. Wara-Aswapati, R. Surarit, A. Chayasadom, J. A. Boch, and W. Pitiphat, “RANKL upregulation associated with periodontitis and porphyromonas gingivalis,” Journal of Periodontology, vol. 78, no. 6, pp. 1062–1069, 2007. View at Publisher · View at Google Scholar · View at Scopus
  157. J. I. Salonen, M. B. Kautsky, and B. A. Dale, “Changes in cell phenotype during regeneration of junctional epithelium of human gingiva in vitro,” Journal of Periodontal Research, vol. 24, no. 6, pp. 370–377, 1989. View at Scopus
  158. J. Oksanen and M. Hormia, “An organotypic in vitro model that mimics the dento-epithelial junction,” Journal of Periodontology, vol. 73, no. 1, pp. 86–93, 2002. View at Publisher · View at Google Scholar · View at Scopus
  159. U. K. Gursoy, M. Pöllänen, E. Könönen, and V.-J. Uitto, “A novel organotypic dento-epithelial culture model: effect of fusobacterium nucleatum biofilm on B-defensin-2, -3, and LL-37 expression,” Journal of Periodontology, vol. 83, no. 2, pp. 242–247, 2012. View at Publisher · View at Google Scholar
  160. B. C. Dickinson, C. E. Moffatt, D. Hagerty et al., “Interaction of oral bacteria with gingival epithelial cell multilayers,” Molecular Oral Microbiology, vol. 26, no. 3, pp. 210–220, 2011. View at Publisher · View at Google Scholar · View at Scopus
  161. C. A. Dinarello, “A clinical perspective of IL-1β as the gatekeeper of inflammation,” European Journal of Immunology, vol. 41, no. 5, pp. 1203–1217, 2011. View at Publisher · View at Google Scholar · View at Scopus
  162. A. Paino, H. Tuominen, M. Jääskeläinen et al., “Trimeric form of intracellular ATP synthase subunit β of aggregatibacter actinomycetemcomitans binds human interleukin-1β,” PLoS ONE, vol. 6, no. 4, Article ID e18929, 2011. View at Publisher · View at Google Scholar · View at Scopus
  163. D. O. Overman and J. I. Salonen, “Characterization of the human junctional epithelial cells directly attached to the tooth (DAT cells) in periodontal disease,” Journal of Dental Research, vol. 73, no. 12, pp. 1818–1823, 1994. View at Scopus
  164. G. Giannelli, J. Falk-Marzillier, O. Schiraldi, W. G. Stetler-Stevenson, and V. Quaranta, “Induction of cell migration by matrix metalloprotease-2 cleavage of laminin-5,” Science, vol. 277, no. 5323, pp. 225–228, 1997. View at Publisher · View at Google Scholar · View at Scopus
  165. V. J. Uitto, K. Airola, M. Vaalamo et al., “Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal epithelium during chronic inflammation,” American Journal of Pathology, vol. 152, no. 6, pp. 1489–1499, 1998. View at Scopus
  166. L. Zhang, L. Koivisto, J. Heino, and V. J. Uitto, “Bacterial heat shock protein 60 may increase epithelial cell migration through activation of MAP kinases and inhibition of α6β4 integrin expression,” Biochemical and Biophysical Research Communications, vol. 319, no. 4, pp. 1088–1095, 2004. View at Publisher · View at Google Scholar · View at Scopus
  167. S. Schluger, “Periodontics today: dentistry tomorrow,” District of Columbia Dental Society Journal, pp. 6–8, 1977. View at Scopus
  168. H. E. Schroeder and M. A. Listgarten, “The gingival tissues: the architecture of periodontal protection,” Periodontology 2000, vol. 14, no. 1, pp. 91–120, 1997. View at Scopus
  169. T. Takata and K. Donath, “The mechanism of pocket formation. A light microscopic study on undecalcified human material,” Journal of Periodontology, vol. 59, no. 4, pp. 215–221, 1988. View at Scopus
  170. D. D. Bosshardt and N. P. Lang, “The junctional epithelium: from health to disease,” Journal of Dental Research, vol. 84, no. 1, pp. 9–20, 2005. View at Publisher · View at Google Scholar · View at Scopus
  171. L. Vitkov, W. D. Krautgartner, and M. Hannig, “Surface morphology of pocket epithelium,” Ultrastructural Pathology, vol. 29, no. 2, pp. 121–127, 2005. View at Publisher · View at Google Scholar · View at Scopus
  172. H. Bantel, T. Beikler, T. F. Flemmig, and K. Schulze-Osthoff, “Caspase activation is involved in chronic periodontitis,” FEBS Letters, vol. 579, no. 25, pp. 559–5564, 2005. View at Publisher · View at Google Scholar · View at Scopus