Table of Contents Author Guidelines Submit a Manuscript
International Journal of Endocrinology
Volume 2014 (2014), Article ID 180304, 13 pages
http://dx.doi.org/10.1155/2014/180304
Research Article

Leptin Effects on the Regenerative Capacity of Human Periodontal Cells

1Experimental Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany
2Clinical Research Unit 208, University of Bonn, 53111 Bonn, Germany
3Department of Diagnosis and Surgery, School of Dentistry, UNESP, 14801-903 Araraquara, SP, Brazil
4Department of Orthodontics, University of Bonn, 53111 Bonn, Germany
5Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, 53111 Bonn, Germany
6Oral Technology, Center of Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany
7Department of Periodontology, Laboratory of Oral Microbiology, University of Bern, 3010 Bern, Switzerland

Received 24 February 2014; Revised 26 June 2014; Accepted 4 July 2014; Published 22 July 2014

Academic Editor: Daniela Jezova

Copyright © 2014 Marjan Nokhbehsaim 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. D. M. Nguyen and H. B. El-Serag, “The epidemiology of obesity,” Gastroenterology Clinics of North America, vol. 39, no. 1, pp. 1–7, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. G. A. Stevens, G. M. Singh, Y. Lu et al., “Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index). National, regional, and global trends in adult overweight and obesity prevalences,” Population Health Metrics, vol. 10, p. 22, 2012. View at Google Scholar
  3. G. B. Mensink, A. Schienkiewitz, M. Haftenberger, T. Lampert, T. Ziese, and C. Scheidt-Nave, “Overweight and obesity in Germany: results of the German health interview and examination survey for adults (DEGS1),” Bundesgesundheitsblatt Gesundheits Forschung Gesundheitsschutz, vol. 56, pp. 786–794, 2013. View at Google Scholar
  4. S. Allender and M. Rayner, “The burden of overweight and obesity-related ill health in the UK,” Obesity Reviews, vol. 8, no. 5, pp. 467–473, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Cawley and C. Meyerhoefer, “The medical care costs of obesity: an instrumental variables approach,” Journal of Health Economics, vol. 31, no. 1, pp. 219–230, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. J. P. Moriarty, M. E. Branda, K. D. Olsen et al., “The effects of incremental costs of smoking and obesity on health care costs among adults: a 7-year longitudinal study,” Journal of Occupational and Environmental Medicine, vol. 54, no. 3, pp. 286–291, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Adamczak and A. Wiecek, “The adipose tissue as an endocrine organ,” Seminars in Nephrology, vol. 33, no. 1, pp. 2–13, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. R. Krysiak, G. Handzlik-Orlik, and B. Okopien, “The role of adipokines in connective tissue diseases,” European Journal of Nutrition, vol. 51, no. 5, pp. 513–528, 2012. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Raucci, F. Rusolo, A. Sharma, G. Colonna, G. Castello, and S. Costantini, “Functional and structural features of adipokine family,” Cytokine, vol. 61, no. 1, pp. 1–14, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. J. van de Voorde, B. Pauwel, C. Boydens, and K. Decaluwé, “Adipocytokines in relation to cardiovascular disease,” Metabolism, vol. 62, pp. 1513–1521, 2013. View at Google Scholar
  11. R. V. Considine, M. K. Sinha, M. L. Heiman et al., “Serum immunoreactive-leptin concentrations in normal-weight and obese humans,” The New England Journal of Medicine, vol. 334, no. 5, pp. 292–295, 1996. View at Publisher · View at Google Scholar · View at Scopus
  12. F. Carbone, C. La Rocca, and G. Matarese, “Immunological functions of leptin and adiponectin,” Biochimie, vol. 94, no. 10, pp. 2082–2088, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. A. la Cava, “Proinflammatory activities of leptin in non-autoimmune conditions,” Inflammation and Allergy-Drug Targets, vol. 11, no. 4, pp. 298–302, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. G. Paz-Filho, C. Mastronardi, C. B. Franco, K. B. Wang, M. Wong, and J. Licinio, “Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications,” Arquivos Brasileiros de Endocrinologia & Metabologia, vol. 56, no. 9, pp. 597–607, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. C. Procaccini, E. Jirillo, and G. Matarese, “Leptin as an immunomodulator,” Molecular Aspects of Medicine, vol. 33, no. 1, pp. 35–45, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. Y. Zhou and L. Rui, “Leptin signaling and leptin resistance,” Frontiers of Medicine, vol. 7, no. 2, pp. 207–222, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. B. W. Chaffee and S. J. Weston, “Association between chronic periodontal disease and obesity: a systematic review and meta-analysis,” Journal of Periodontology, vol. 81, no. 12, pp. 1708–1724, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Suvan, F. D'Aiuto, D. R. Moles, A. Petrie, and N. Donos, “Association between overweight/obesity and periodontitis in adults: a systematic review,” Obesity Reviews, vol. 12, no. 501, pp. e381–e404, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. B. L. Pihlstrom, B. S. Michalowicz, and N. W. Johnson, “Periodontal diseases,” The Lancet, vol. 366, no. 9499, pp. 1809–1820, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. L. Sbordone and C. Bortolaia, “Oral microbial biofilms and plaque-related diseases: microbial communities and their role in the shift from oral health to disease,” Clinical Oral Investigations, vol. 7, no. 4, pp. 181–188, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. 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
  22. T. Yucel-Lindberg and T. Båge, “Inflammatory mediators in the pathogenesis of periodontitis,” Expert Reviews in Molecular Medicine, vol. 15, no. e7, 22 pages, 2013. View at Publisher · View at Google Scholar
  23. L. J. A. Heitz-Mayfield, “How effective is surgical therapy compared with nonsurgical debridement?” Periodontology 2000, vol. 37, pp. 72–87, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. M. K. McGuire and D. L. Cochran, “Evaluation of human recession defects treated with coronally advanced flaps and either enamel matrix derivative or connective tissue. Part 2: histological evaluation,” Journal of Periodontology, vol. 74, no. 8, pp. 1126–1135, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Sculean, R. Alessandri, R. Miron, G. E. Salvi, and D. D. Bosshardt, “Enamel matrix proteins and periodontal wound healing and regeneration,” Clinical Advances in Periodontics, vol. 1, pp. 101–117, 2011. View at Google Scholar
  26. R. A. Yukna and J. T. Mellonig, “Histologic evaluation of periodontal healing in humans following regenerative therapy with enamel matrix derivative. A 10-case series,” Journal of Periodontology, vol. 71, no. 5, pp. 752–759, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. D. D. Bosshardt, “Biological mediators and periodontal regeneration: a review of enamel matrix proteins at the cellular and molecular levels,” Journal of Clinical Periodontology, vol. 35, no. 8, pp. 87–105, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. H. M. Grandin, A. C. Gemperli, and M. Dard, “Enamel matrix derivative: a review of cellular effects in vitro and a model of molecular arrangement and functioning,” Tissue Engineering B: Reviews, vol. 18, no. 3, pp. 181–202, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. D. L. Johnson, D. Carnes, B. Steffensen, and D. L. Cochran, “Cellular effects of enamel matrix derivative are associated with different molecular weight fractions following separation by size-exclusion chomatography,” Journal of Periodontology, vol. 80, no. 4, pp. 648–656, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. S. Suzuki, T. Nagano, Y. Yamakoshi et al., “Enamel matrix derivative gel stimulates signal transduction of BMP and TGF-β,” Journal of Dental Research, vol. 84, no. 6, pp. 510–514, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Okubo, M. Kobayashi, T. Takiguchi et al., “Participation of endogenous IGF-I and TGF-β1 with enamel matrix derivative-stimulated cell growth in human periodontal ligament cells,” Journal of Periodontal Research, vol. 38, no. 1, pp. 1–9, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. S. S. Prime, M. Pring, M. Davies, and I. C. Paterson, “TGF-β signal transduction in oro-facial health and non-malignant disease (part I),” Critical Reviews in Oral Biology & Medicine, vol. 15, no. 6, pp. 324–336, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. C. Sieber, J. Kopf, C. Hiepen, and P. Knaus, “Recent advances in BMP receptor signaling,” Cytokine and Growth Factor Reviews, vol. 20, no. 5-6, pp. 343–355, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. J. Deschner and M. Nokhbehsaim, “Regulatory effects of inflammatory and biomechanical signals on regenerative periodontal healing,” International Journal of Oral & Maxillofacial Implants, vol. 28, no. 6, pp. e472–e477, 2013. View at Google Scholar
  35. H. Inaba, S. Kawai, K. Nakayama, N. Okahashi, and A. Amano, “Effect of enamel matrix derivative on periodontal ligament cells in vitro is deminished by porphyromonas gingivalis,” Journal of Periodontology, vol. 75, no. 6, pp. 858–865, 2004. View at Publisher · View at Google Scholar · View at Scopus
  36. H. Inaba, M. Tagashira, T. Kanda, T. Ohno, S. Kawai, and A. Amano, “Apple- and hop-polyphenols protect periodontal ligament cells stimulated with enamel matrix derivative from Porphyromonas gingivalis,” Journal of Periodontology, vol. 76, no. 12, pp. 2223–2229, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Suvan, A. Petrie, D. R. Moles et al., “Body mass index as a predictive factor of periodontal therapy outcomes,” Journal of Dental Research, vol. 93, pp. 49–54, 2014. View at Publisher · View at Google Scholar
  38. D. Lakkis, N. F. Bissada, A. Saber et al., “Response to periodontal therapy in patients who had weight loss after bariatric surgery and obese counterparts: a pilot study,” Journal of Periodontology, vol. 83, no. 6, pp. 684–689, 2012. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Mariotti and D. L. Cochran, “Characterization of fibroblasts derived from human periodontal ligament and gingiva,” Journal of Periodontology, vol. 61, no. 2, pp. 103–111, 1990. View at Publisher · View at Google Scholar · View at Scopus
  40. E. K. Basdra and G. Komposch, “Osteoblast-like properties of human periodontal ligament cells: an in vitro analysis,” European Journal of Orthodontics, vol. 19, no. 6, pp. 615–621, 1997. View at Google Scholar · View at Scopus
  41. G. S. Zimmermann, M. F. Bastos, T. E. D. Gonçalves, L. Chambrone, and P. M. Duarte, “Local and circulating levels of adipocytokines in obese and normal weight individuals with chronic periodontitis,” Journal of Periodontology, vol. 84, no. 5, pp. 624–633, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Damanaki, M. Nokhbehsaim, S. Eick et al., “Regulation of NAMPT in human gingival fibroblasts and biopsies,” Mediators of Inflammation, vol. 2014, Article ID 912821, 10 pages, 2014. View at Publisher · View at Google Scholar
  43. A. V. B. Nogueira, M. Nokhbehsaim, S. Eick et al., “Regulation of visfatin by microbial and biomechanical signals in PDL cells,” Clinical Oral Investigations, vol. 18, no. 1, pp. 171–178, 2014. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Nokhbehsaim, J. Winter, B. Rath, A. Jäger, S. Jepsen, and J. Deschner, “Effects of enamel matrix derivative on periodontal wound healing in an inflammatory environment in vitro,” Journal of Clinical Periodontology, vol. 38, no. 5, pp. 479–490, 2011. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Nokhbehsaim, B. Deschner, C. Bourauel et al., “Interactions of enamel matrix derivative and biomechanical loading in periodontal regenerative healing,” Journal of Periodontology, vol. 82, no. 12, pp. 1725–1734, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Nokhbehsaim, S. Eick, A. V. B. Nogueira et al., “Stimulation of MMP-1 and CCL2 by NAMPT in PDL cells,” Mediators of Inflammation, vol. 2013, Article ID 437123, 12 pages, 2013. View at Publisher · View at Google Scholar
  47. M. Nokhbehsaim, S. Keser, A. Jäger, S. Jepsen, and J. Deschner, “Regulation of regenerative periodontal healing by NAMPT,” Mediators of Inflammation, vol. 2013, Article ID 202530, 11 pages, 2013. View at Publisher · View at Google Scholar
  48. A. M. Byrne, D. J. Bouchier-Hayes, and J. H. Harmey, “Angiogenic and cell survival functions of Vascular Endothelial Growth Factor (VEGF),” Journal of Cellular and Molecular Medicine, vol. 9, no. 4, pp. 777–794, 2005. View at Publisher · View at Google Scholar · View at Scopus
  49. M. M. Deckers, M. Karperien, C. van der Bent, T. Yamashita, S. E. Papapoulos, and C. W. Löwik, “Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation,” Endocrinology, vol. 141, no. 5, pp. 1667–1674, 2000. View at Publisher · View at Google Scholar · View at Scopus
  50. N. Ferrara, “Role of vascular endothelial growth factor in the regulation of angiogenesis,” Kidney International, vol. 56, no. 3, pp. 794–814, 1999. View at Publisher · View at Google Scholar · View at Scopus
  51. M. R. Sierra-Honigmann, A. K. Nath, C. Murakami et al., “Biological action of leptin as an angiogenic factor,” Science, vol. 281, no. 5383, pp. 1683–1686, 1998. View at Publisher · View at Google Scholar · View at Scopus
  52. R. R. Gonzalez, S. Cherfils, M. Escobar et al., “Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2),” The Journal of Biological Chemistry, vol. 281, no. 36, pp. 26320–26328, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. R. B. Johnson and F. G. Serio, “Leptin within healthy and diseased human gingiva,” Journal of Periodontology, vol. 72, no. 9, pp. 1254–1257, 2001. View at Publisher · View at Google Scholar · View at Scopus
  54. Y. Seomun, J.-T. Kim, and C.-K. Joo, “MMP-14 mediated MMP-9 expression is involved in TGF-beta1-induced keratinocyte migration,” Journal of Cellular Biochemistry, vol. 104, no. 3, pp. 934–941, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. P. Sysa, J. J. Potter, X. Liu, and E. Mezey, “Transforming growth factor-β1 up-regulation of human α1(I) collagen is mediated by Sp1 and Smad2 transacting factors,” DNA and Cell Biology, vol. 28, no. 9, pp. 425–434, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. M. Valluru, C. A. Staton, M. W. R. Reed, and N. J. Brown, “Transforming growth factor-β and endoglin signaling orchestrate wound healing,” Frontiers in Physiology, vol. 2, Article 89, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. D. W. Hamilton, “Functional role of periostin in development and wound repair: implications for connective tissue disease,” Journal of Cell Communication and Signaling, vol. 2, no. 1-2, pp. 9–17, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. H. F. Rios, D. Ma, Y. Xie et al., “Periostin is essential for the integrity and function of the periodontal ligament during occlusal loading in mice,” Journal of Periodontology, vol. 79, no. 8, pp. 1480–1490, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. G. E. Romanos, K. P. Asnani, D. Hingorani, and V. L. Deshmukh, “PERIOSTIN: role in formation and maintenance of dental tissues,” Journal of Cellular Physiology, vol. 229, pp. 1–5, 2014. View at Google Scholar
  60. P. J. Marie, “Transcription factors controlling osteoblastogenesis,” Archives of Biochemistry and Biophysics, vol. 473, no. 2, pp. 98–105, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. M. Nokhbehsaim, B. Deschner, J. Winter et al., “Interactions of regenerative, inflammatory and biomechanical signals on bone morphogenetic protein-2 in periodontal ligament cells,” Journal of Periodontal Research, vol. 46, no. 3, pp. 374–381, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. V. Gangadhar, A. Ramesh, and B. Thomas, “Correlation between leptin and the health of the gingiva: a predictor of medical risk,” Indian Journal of Dental Research, vol. 22, no. 4, pp. 537–541, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. R. Gundala, V. K. Chava, and K. Ramalingam, “Association of leptin in periodontitis and acute myocardial infarction,” Journal of Periodontology, vol. 85, no. 7, pp. 917–924, 2012. View at Publisher · View at Google Scholar
  64. L. Kardeşler, N. Buduneli, Ş. Çetinkalp, and D. F. Kinane, “Adipokines and inflammatory mediators after initial periodontal treatment in patients with type 2 diabetes and chronic periodontitis,” Journal of Periodontology, vol. 81, no. 1, pp. 24–33, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. Y. Shimada, Y. Komatsu, I. Ikezawa-Suzuki, H. Tai, N. Sugita, and H. Yoshie, “The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein,” Journal of Periodontology, vol. 81, no. 8, pp. 1118–1123, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. B. V. Karthikeyan and A. R. Pradeep, “Leptin levels in gingival crevicular fluid in periodontal health and disease,” Journal of Periodontal Research, vol. 42, no. 4, pp. 300–304, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. B. V. Karthikeyan and A. R. Pradeep, “Gingival crevicular fluid and serum leptin: their relationship to periodontal health and disease,” Journal of Clinical Periodontology, vol. 34, no. 6, pp. 467–472, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. F. Y. Bozkurt, Z. Yetkin Ay, R. Sütçü, N. Delibaş, and R. Demirel, “Gingival crevicular fluid leptin levels in periodontitis patients with long-term and heavy smoking,” Journal of Periodontology, vol. 77, no. 4, pp. 634–640, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Dilsiz, N. Kiliç, T. Aydin, F. Nesibe Ates, M. Zihni, and C. Bulut, “Leptin levels in gingival crevicular fluid during orthodontic tooth movement,” Angle Orthodontist, vol. 80, no. 3, pp. 504–508, 2010. View at Publisher · View at Google Scholar · View at Scopus
  70. Z. Y. Ay, F. Y. Kirziogğlu, M. O. Tonguç, R. Sütçü, and N. Kapucuoğlu, “The gingiva contains leptin and leptin receptor in health and disease,” Odontology, vol. 100, no. 2, pp. 222–231, 2012. View at Google Scholar
  71. W. Li, W. Zhu, J. Hou, B. Huang, K. Liu, and H. Meng, “Leptin and its receptor expression in dental and periodontal tissues of primates,” Cell and Tissue Research, vol. 355, pp. 181–188, 2014. View at Publisher · View at Google Scholar
  72. H. Gottschling-Zeller, M. Birgel, D. Scriba, W. F. Blum, and H. Hauner, “Depot-specific release of leptin from subcutaneous and omental adipocytes in suspension culture: effect of tumor necrosis factor-α and transforming growth factor-β1,” European Journal of Endocrinology, vol. 141, no. 4, pp. 436–442, 1999. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Grosfeld, V. Zilberfarb, S. Turban, J. André, M. Guerre-Millo, and T. Issad, “Hypoxia increases leptin expression in human PAZ6 adipose cells,” Diabetologia, vol. 45, no. 4, pp. 527–530, 2002. View at Publisher · View at Google Scholar · View at Scopus
  74. L. B. Williams, R. L. Fawcett, A. S. Waechter et al., “Leptin production in adipocytes from morbidly obese subjects: stimulation by dexamethasone, inhibition with troglitazone, and influence of gender,” The Journal of Clinical Endocrinology & Metabolism, vol. 85, no. 8, pp. 2678–2684, 2000. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Hoffsted, P. Eriksson, S. Mottagui-Tabar, and P. Arner, “A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin,” Hormone and Metabolic Research, vol. 34, no. 7, pp. 355–359, 2002. View at Publisher · View at Google Scholar · View at Scopus
  76. S. J. Kim, “Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-α: in monocyte-derived macrophages,” Journal of Periodontal & Implant Science, vol. 40, no. 3, pp. 119–124, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Honig, C. Rordorf-Adam, C. Siegmund, W. Wiedemann, and F. Erard, “Increased interleukin-1-beta (IL-1β) concentration in gingival tissue from periodontitis patients,” Journal of Periodontal Research, vol. 24, no. 6, pp. 362–367, 1989. View at Publisher · View at Google Scholar · View at Scopus
  78. L. T. Hou, C. M. Liu, and W. K. Chang, “Increased interleukin-1 beta levels in gingival crevicular fluid of Chinese periodontal patients,” Journal of the Formosan Medical Association, vol. 93, no. 2, pp. 99–103, 1994. View at Google Scholar · View at Scopus
  79. A. Mathur, B. Michalowicz, M. Castillo, and D. Aeppli, “Interleukin-1 alpha, interleukin-8 and interferon-alpha levels in gingival crevicular fluid,” Journal of Periodontal Research, vol. 31, no. 7, pp. 489–495, 1996. View at Publisher · View at Google Scholar · View at Scopus
  80. S. C. Holt and J. L. Ebersole, “Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the “red complex”, a prototype polybacterial pathogenic consortium in periodontitis,” Periodontology 2000, vol. 38, pp. 72–122, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. K. Nakayama, “Molecular genetics of Porphyromonas gingivalis: gingipains and other virulence factors,” Current Protein and Peptide Science, vol. 4, no. 6, pp. 389–395, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Potempa, A. Sroka, T. Imamura, and J. Travis, “Gingipains, the major cysteine proteinases and virulence factors of Porphyromonas gingivalis: structure, function and assembly of multidomain protein complexes,” Current Protein and Peptide Science, vol. 4, no. 6, pp. 397–407, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. Y. W. Han, W. Shi, G. T. Huang et al., “Interactions between periodontal bacteria and human oral epithelial cells: fusobacterium nucleatum adheres to and invades epithelial cells,” Infection and Immunity, vol. 68, no. 6, pp. 3140–3146, 2000. View at Publisher · View at Google Scholar · View at Scopus
  84. J. He, W. Huang, Z. Pan et al., “Quantitative analysis of microbiota in saliva, supragingival, and subgingival plaque of Chinese adults with chronic periodontitis,” Clinical Oral Investigations, vol. 16, no. 6, pp. 1579–1588, 2012. View at Publisher · View at Google Scholar · View at Scopus
  85. B. Signat, C. Roques, P. Poulet, and D. Duffaut, “Fusobacterium nucleatum in periodontal health and disease,” Current Issues in Molecular Biology, vol. 13, no. 2, pp. 25–36, 2011. View at Google Scholar · View at Scopus
  86. M. Nokhbehsaim, B. Deschner, J. Winter et al., “Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1β in vitro,” Clinical Oral Investigations, vol. 16, no. 1, pp. 275–283, 2012. View at Publisher · View at Google Scholar · View at Scopus