Top

Published in:

01-01-2014 | Original Article

Regulation of visfatin by microbial and biomechanical signals in PDL cells

Authors: Andressa Vilas Boas Nogueira, Marjan Nokhbehsaim, Sigrun Eick, Christoph Bourauel, Andreas Jäger, Søren Jepsen, Joni Augusto Cirelli, James Deschner

Published in: Clinical Oral Investigations | Issue 1/2014

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.

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

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 7:181–188PubMedCrossRef

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

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):1575–1584PubMedCrossRef

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

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 72:495–505PubMedCrossRef

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

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 103:313–319PubMedCrossRef

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 31:529–535PubMedCrossRef

10.

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

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 90:793–798PubMedCrossRef

12.

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

13.

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

14.

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

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 37:413–420PubMedCrossRef

16.

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

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

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 152:3155–3164PubMedCrossRef

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) 33:465–472CrossRef

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 178:1748–1758PubMed

21.

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

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 27:515–527PubMedCrossRef

23.

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

24.

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

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 91:295–299PubMedCrossRef

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 91:1578–1581PubMedCrossRef

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 54:2911–2916PubMedCrossRef

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 82:1314–1319PubMedCrossRef

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 83:629–634PubMedCrossRef

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 32:383–388PubMedCrossRef

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 71:390–402PubMedCrossRef

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 82:1725–1734PubMedCrossRef

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 46:374–381PubMedCrossRef

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 16:275–283PubMedCrossRef

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 20:275–281PubMed

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 32:229–243PubMedCrossRef

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 283:34833–34843PubMedCrossRef

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 113:1318–1327PubMedCentralPubMed

39.

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

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):1579–8PubMedCrossRef

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 80:1174–1183PubMedCrossRef

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 77:1044–1052PubMedCentralPubMedCrossRef

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 68:3140–3146PubMedCentralPubMedCrossRef

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 54:349–355PubMedCrossRef

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 17:899–901PubMed

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 80:1416–1420PubMedCrossRef

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 72:1102–1113PubMedCrossRef

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 70:218–225PubMedCentralPubMedCrossRef

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 69:12–20PubMedCrossRef

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 27:333–339PubMedCrossRef

51.

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

Title: Regulation of visfatin by microbial and biomechanical signals in PDL cells
Authors: Andressa Vilas Boas Nogueira
Marjan Nokhbehsaim
Sigrun Eick
Christoph Bourauel
Andreas Jäger
Søren Jepsen
Joni Augusto Cirelli
James Deschner
Publication date: 01-01-2014
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 1/2014
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-013-0935-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Regulation of visfatin by microbial and biomechanical signals in PDL cells

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Please log in to get access to this content

Other articles of this Issue 1/2014

Tissue engineering strategies for alveolar cleft reconstruction: a systematic review of the literature

Can preoperative imaging help to predict postoperative outcome after wisdom tooth removal? A randomized controlled trial using panoramic radiography versus cone-beam CT

Effect of decreased implant healing time on bone (re)modeling adjacent to plateaued implants under functional loading in a dog model

A histomorphometric analysis of the nature of the mandibular canal in the anterior molar region

Oral and genital HPV genotypic concordance between sexual partners

3D analyses of interface voids in root canals filled with different sealer materials in combination with warm gutta-percha technique