Skip to main content

Advertisement

SpringerLink
Log in

Regulation of visfatin by microbial and biomechanical signals in PDL cells

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

This in vitro study was established to examine whether visfatin thought to be a link between periodontitis and obesity is produced by periodontal ligament (PDL) cells and, if so, whether its synthesis is modulated by microbial and/or biomechanical signals.

Materials and methods

PDL cells seeded on BioFlex® plates were exposed to the oral pathogen Fusobacterium nucleatum ATCC 25586 and/or subjected to biomechanical strain for up to 3 days. Gene expression of visfatin and toll-like receptors (TLR) 2 and 4 was analyzed by RT-PCR, visfatin protein synthesis by ELISA and immunocytochemistry, and NFκB nuclear translocation by immunofluorescence.

Results

F. nucleatum upregulated the visfatin expression in a dose- and time-dependent fashion. Preincubation with neutralizing antibodies against TLR2 and TLR4 caused a significant inhibition of the F. nucleatum-upregulated visfatin expression at 1 day. F. nucleatum stimulated the NFκB nuclear translocation. Biomechanical loading reduced the stimulatory effects of F. nucleatum on visfatin expression at 1 and 3 days and also abrogated the F. nucleatum-induced NFκB nuclear translocation at 60 min. Biomechanical loading inhibited significantly the expression of TLR2 and TLR4 at 3 days. The regulatory effects of F. nucleatum and/or biomechanical loading on visfatin expression were also observed at protein level.

Conclusions

PDL cells produce visfatin, and this production is enhanced by F. nucleatum. Biomechanical loading seems to be protective against the effects of F. nucleatum on visfatin expression.

Clinical relevance

Visfatin produced by periodontal tissues could play a major role in the pathogenesis of periodontitis and the interactions with obesity and other systemic diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809–1820

    Article  PubMed  Google Scholar 

  2. Sbordone L, Bortolaia C (2003) Oral microbial biofilms and plaque-related diseases: microbial communities and their role in the shift from oral health to disease. Clin Oral Investig 7:181–188

    Article  PubMed  Google Scholar 

  3. Seymour GJ, Ford PJ, Cullinan MP, Leishman S, Yamazaki K (2007) Relationship between periodontal infections and systemic disease. Clin Microbiol Infect 13(Suppl 4):3–10

    Article  PubMed  Google Scholar 

  4. Naveh GR, Lev-Tov Chattah N, Zaslansky P, Shahar R, Weiner S (2012) Tooth-PDL-bone complex: response to compressive loads encountered during mastication—a review. Arch Oral Biol 57(12):1575–1584

    Article  PubMed  Google Scholar 

  5. McCulloch CA, Lekic P, McKee MD (2000) Role of physical forces in regulating the form and function of the periodontal ligament. Periodontol 24:56–72

    Article  Google Scholar 

  6. Harrel SK, Nunn ME (2001) The effect of occlusal discrepancies on periodontitis. II. Relationship of occlusal treatment to the progression of periodontal disease. J Periodontol 72:495–505

    Article  PubMed  Google Scholar 

  7. Nunn ME, Harrel SK (2001) The effect of occlusal discrepancies on periodontitis. I. Relationship of initial occlusal discrepancies to initial clinical parameters. J Periodontol 72:485–494

    Article  PubMed  Google Scholar 

  8. Wennström JL, Stokland BL, Nyman S, Thilander B (1993) Periodontal tissue response to orthodontic movement of teeth with infrabony pockets. Am J Orthod Dentofacial Orthop 103:313–319

    Article  PubMed  Google Scholar 

  9. Bildt MM, Bloemen M, Kuijpers-Jagtman AM, Von den Hoff JW (2009) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in gingival crevicular fluid during orthodontic tooth movement. Eur J Orthod 31:529–535

    Article  PubMed  Google Scholar 

  10. Ren Y, Vissink A (2008) Cytokines in crevicular fluid and orthodontic tooth movement. Eur J Oral Sci 116:89–97

    Article  PubMed  Google Scholar 

  11. Goto KT, Kajiya H, Nemoto T, Tsutsumi T, Tsuzuki T, Sato H, Okabe K (2011) Hyperocclusion stimulates osteoclastogenesis via CCL2 expression. J Dent Res 90:793–798

    Article  PubMed  Google Scholar 

  12. Chaffee BW, Weston SJ (2010) Association between chronic periodontal disease and obesity: a systematic review and meta-analysis. J Periodontol 81:1708–1724

    Article  PubMed Central  PubMed  Google Scholar 

  13. Johnson AR, Justin Milner J, Makowski L (2012) The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol Rev 249:218–238

    Article  PubMed Central  PubMed  Google Scholar 

  14. Rasouli N, Kern PA (2008) Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93:64–73

    Article  Google Scholar 

  15. Conde J, Scotece M, Gómez R, López V, Gómez-Reino JJ, Lago F, Gualillo O (2011) Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. Biofactors 37:413–420

    Article  PubMed  Google Scholar 

  16. Inadera H (2008) The usefulness of circulating adipokine levels for the assessment of obesity-related health problems. Int J Med Sci 5:248–262

    Article  PubMed Central  PubMed  Google Scholar 

  17. Preshaw PM, Foster N, Taylor JJ (2007) Cross-susceptibility between periodontal disease and type 2 diabetes mellitus: an immunobiological perspective. Periodontol 2000 45:138-157

    Google Scholar 

  18. Kanda N, Hau CS, Tada Y, Tatsuta A, Sato S, Watanabe S (2011) Visfatin enhances CXCL8, CXCL10, and CCL20 production in human keratinocytes. Endocrinology 152:3155–3164

    Article  PubMed  Google Scholar 

  19. Lee WJ, Wu CS, Lin H, Lee IT, Wu CM, Tseng JJ, Chou MM, Sheu WH (2009) Visfatin-induced expression of inflammatory mediators in human endothelial cells through the NF-kappaB pathway. Int J Obes (Lond) 33:465–472

    Article  Google Scholar 

  20. Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H (2007) Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 178:1748–1758

    PubMed  Google Scholar 

  21. Taşkesen D, Kirel B, Us T (2012) Serum visfatin levels, adiposity and glucose metabolism in obese adolescents. J Clin Res Pediatr Endocrinol 4:76–81

    Article  PubMed Central  PubMed  Google Scholar 

  22. Chang YH, Chang DM, Lin KC, Shin SJ, Lee YJ (2011) Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev 27:515–527

    Article  PubMed  Google Scholar 

  23. Zhang LQ, Heruth DP, Ye SQ (2011) Nicotinamide phosphoribosyltransferase in Human Diseases. J Bioanal Biomed 3:13–25

    Article  PubMed  Google Scholar 

  24. Saddi-Rosa P, Oliveira CS, Giuffrida FM, Reis AF (2010) Visfatin, glucose metabolism and vascular disease: a review of evidence. Diabetol Metab Syndr 2:21

    Article  PubMed Central  PubMed  Google Scholar 

  25. Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ (2006) Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 91:295–299

    Article  PubMed  Google Scholar 

  26. Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B (2006) Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. J Clin Endocrinol Metab 91:1578–1581

    Article  PubMed  Google Scholar 

  27. Berndt J, Klöting N, Kralisch S, Kovacs P, Fasshauer M, Schön MR, Stumvoll M, Blüher M (2005) Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 54:2911–2916

    Article  PubMed  Google Scholar 

  28. Pradeep AR, Raghavendra NM, Prasad MV, Kathariya R, Patel SP, Sharma A (2011) Gingival crevicular fluid and serum visfatin concentration: their relationship in periodontal health and disease. J Periodontol 82:1314–1319

    Article  PubMed  Google Scholar 

  29. Pradeep AR, Raghavendra NM, Sharma A, Patel SP, Raju A, Kathariya R, Rao NS, Naik SB (2012) Association of serum and crevicular visfatin levels in periodontal health and disease with type 2 diabetes mellitus. J Periodontol 83:629–634

    Article  PubMed  Google Scholar 

  30. Raghavendra NM, Pradeep AR, Kathariya R, Sharma A, Rao NS, Naik SB (2012) Effect of non-surgical periodontal therapy on gingival crevicular fluid and serum visfatin concentration in periodontal health and disease. Dis Markers 32:383–388

    Article  PubMed  Google Scholar 

  31. Nokhbehsaim M, Deschner B, Winter J, Reimann S, Bourauel C, Jepsen S, Jäger A, Deschner J (2010) Contribution of orthodontic load to inflammation-mediated periodontal destruction. J Orofac Orthop 71:390–402

    Article  PubMed  Google Scholar 

  32. Nokhbehsaim M, Deschner B, Bourauel C, Reimann S, Winter J, Rath B, Jäger A, Jepsen S, Deschner J (2011) Interactions of enamel matrix derivative and biomechanical loading in periodontal regenerative healing. J Periodontol 82:1725–1734

    Article  PubMed  Google Scholar 

  33. Nokhbehsaim M, Deschner B, Winter J, Bourauel C, Rath B, Jäger A, Jepsen S, Deschner J (2011) Interactions of regenerative, inflammatory and biomechanical signals on bone morphogenetic protein-2 in periodontal ligament cells. J Periodontal Res 46:374–381

    Article  PubMed  Google Scholar 

  34. Nokhbehsaim M, Deschner B, Winter J, Bourauel C, Jäger A, Jepsen S, Deschner J (2012) Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1β in vitro. Clin Oral Investig 16:275–283

    Article  PubMed  Google Scholar 

  35. Lee KJ, Shin YA, Lee KY, Jun TW, Song W (2010) Aerobic exercise training-induced decrease in plasma visfatin and insulin resistance in obese female adolescents. Int J Sport Nutr Exerc Metab 20:275–281

    PubMed  Google Scholar 

  36. Dahl TB, Holm S, Aukrust P, Halvorsen B (2012) Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology and pathophysiology. Annu Rev Nutr 32:229–243

    Article  PubMed  Google Scholar 

  37. Li Y, Zhang Y, Dorweiler B, Cui D, Wang T, Woo CW, Brunkan CS, Wolberger C, Imai S, Tabas I (2008) Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism. J Biol Chem 283:34833–34843

    Article  PubMed  Google Scholar 

  38. Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC (2004) Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 113:1318–1327

    PubMed Central  PubMed  Google Scholar 

  39. Signat B, Roques C, Poulet P, Duffaut D (2011) Fusobacterium nucleatum in periodontal health and disease. Curr Issues Mol Biol 13:25–36

    PubMed  Google Scholar 

  40. He J, Huang W, Pan Z, Cui H, Qi G, Zhou X, Chen H (2011) Quantitative analysis of microbiota in saliva, supragingival, and subgingival plaque of Chinese adults with chronic periodontitis. Clin Oral Investig 16(6):1579–8

    Article  PubMed  Google Scholar 

  41. Dabija-Wolter G, Cimpan MR, Costea DE, Johannessen AC, Sørnes S, Neppelberg E, Al-Haroni M, Skaug N, Bakken V (2009) Fusobacterium nucleatum enters normal human oral fibroblasts in vitro. J Periodontol 80:1174–1183

    Article  PubMed  Google Scholar 

  42. Ji S, Shin JE, Kim YS, Oh JE, Min BM, Choi Y (2009) Toll-like receptor 2 and NALP2 mediate induction of human beta-defensins by Fusobacterium nucleatum in gingival epithelial cells. Infect Immun 77:1044–1052

    Article  PubMed Central  PubMed  Google Scholar 

  43. Han YW, Shi W, Huang GT, Kinder Haake S, Park NH, Kuramitsu H, Genco RJ (2000) Interactions between periodontal bacteria and human oral epithelial cells: Fusobacterium nucleatum adheres to and invades epithelial cells. Infect Immun 68:3140–3146

    Article  PubMed Central  PubMed  Google Scholar 

  44. Saito A, Inagaki S, Kimizuka R, Okuda K, Hosaka Y, Nakagawa T, Ishihara K (2008) Fusobacterium nucleatum enhances invasion of human gingival epithelial and aortic endothelial cells by Porphyromonas gingivalis. FEMS Immunol Med Microbiol 54:349–355

    Article  PubMed  Google Scholar 

  45. Agarwal S, Long P, Seyedain A, Piesco N, Shree A, Gassner R (2003) A central role for the nuclear factor-kappaB pathway in anti-inflammatory and proinflammatory actions of mechanical strain. FASEB J 17:899–901

    PubMed  Google Scholar 

  46. Long P, Hu J, Piesco N, Buckley M, Agarwal S (2001) Low magnitude of tensile strain inhibits IL-1beta-dependent induction of pro-inflammatory cytokines and induces synthesis of IL-10 in human periodontal ligament cells in vitro. J Dent Res 80:1416–1420

    Article  PubMed  Google Scholar 

  47. Doyle SL, O'Neill LA (2006) Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. Biochem Pharmacol 72:1102–1113

    Article  PubMed  Google Scholar 

  48. Yoshimura A, Kaneko T, Kato Y, Golenbock DT, Hara Y (2002) Lipopolysaccharides from periodontopathic bacteria Porphyromonas gingivalis and Capnocytophaga ochracea are antagonists for human toll-like receptor 4. Infect Immun 70:218–225

    Article  PubMed Central  PubMed  Google Scholar 

  49. Eick S, Straube A, Guentsch A, Pfister W, Jentsch H (2011) Comparison of real-time polymerase chain reaction and DNA-strip technology in microbiological evaluation of periodontitis treatment. Diagn Microbiol Infect Dis 69:12–20

    Article  PubMed  Google Scholar 

  50. Ziegler A, Keilig L, Kawarizadeh A, Jäger A, Bourauel C (2005) Numerical simulation of the biomechanical behaviour of multi-rooted teeth. Eur J Orthod 27:333–339

    Article  PubMed  Google Scholar 

  51. Toms SR, Dakin GJ, Lemons JE, Eberhardt AW (2002) Quasi-linear viscoelastic behavior of the human periodontal ligament. J Biomech 35:1411–1415

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from São Paulo Research Foundation (FAPESP: 2010/07771-4, 2011/13752-5), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES: 2385-11-2), the German Research Foundation (DFG: KFO208/TP4), and the Medical Faculty of the University of Bonn. We would like to thank Ms. Ramona Hömig, Dr. Susanne Reimann, and Prof. Werner Götz for their great support.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Univ Estadual Paulista -- UNESP, Araraquara, Brazil

    Andressa Vilas Boas Nogueira & Joni Augusto Cirelli

  2. Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany

    Andressa Vilas Boas Nogueira, Marjan Nokhbehsaim & James Deschner

  3. Clinical Research Unit 208, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Welschnonnenstrasse 17, 53111, Bonn, Germany

    Marjan Nokhbehsaim, Christoph Bourauel, Andreas Jäger, Søren Jepsen & James Deschner

  4. Department of Periodontology, Laboratory of Oral Microbiology, University of Bern, Bern, Switzerland

    Sigrun Eick

  5. Oral Technology, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany

    Christoph Bourauel

  6. Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany

    Andreas Jäger

  7. Department of Periodontology, Operative and Preventive Dentistry, Center of Dento- Maxillo-Facial Medicine, University of Bonn, Bonn, Germany

    Søren Jepsen

Authors
  1. Andressa Vilas Boas Nogueira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marjan Nokhbehsaim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sigrun Eick
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christoph Bourauel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andreas Jäger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Søren Jepsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joni Augusto Cirelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. James Deschner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James Deschner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nogueira, A.V.B., Nokhbehsaim, M., Eick, S. et al. Regulation of visfatin by microbial and biomechanical signals in PDL cells. Clin Oral Invest 18, 171–178 (2014). https://doi.org/10.1007/s00784-013-0935-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-013-0935-1

Keywords

Search

Navigation