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Orthodontic forces add to nicotine-induced loss of periodontal bone

An in vivo and in vitro study

Kieferorthopädische Kräfte verstärken nikotininduzierten parodontalen Knochenverlust

In-vivo- und In-vitro-Studie

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Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie Aims and scope Submit manuscript

Abstract

Objectives

Nicotine is considered an etiologic factor for chronic inflammatory phenomena within the periodontal ligament that may result in loss of periodontal attachment. Considering that smokers account for 26 % of adult and 12 % of adolescent patients in orthodontic practice, we performed in vivo and in vitro studies as to whether orthodontic forces may add to the nicotine-induced loss of periodontal bone.

Methods

Fourteen male rats (Fischer 344 inbred) were used. Seven of these served as controls, while the other seven received daily subcutaneous injections of 1.89 mg L-nicotine per kg body weight. Both groups were exposed to orthodontic mesialization of the first two upper left molars using a NiTi closed-coil spring, the contralateral side serving as control. Periodontal bone loss was assessed by cone-beam computed tomography (CBCT). Human periodontal fibroblasts were stressed by compression (2 g/cm2) and/or nicotine (3/5/7.5 µmol), and the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-6 (IL-6), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL) was determined at the transcriptional level by quantitative real-time polymerase chain reaction (qRT-PCR) and at the translational level by enzyme-linked immunosorbent assay (ELISA). In addition, differentiation of co-cultured murine RAW264.7 cells to osteoclast-like cells was quantified by tartrate-resistant acid phosphatase (TRAP) staining.

Results

Orthodontic force application in vivo led to a significant increase in nicotine-induced periodontal bone loss, and cell compression in vitro to increased COX-2, PGE2, IL-6, and RANKL expression, reduced OPG expression, and enhanced differentiation of RAW264.7 cells to osteoclast-like cells compared to nicotine alone.

Conclusion

Additional loss of periodontal bone must be expected during orthodontic treatment of smokers. Clinicians should inform their patients of this increased risk and refrain from performing tooth movements before cessation of smoking.

Zusammenfassung

Zielsetzung

Nikotin gilt als ein ätiologischer Faktor chronisch entzündlicher Prozesse im Zahnhalteapparat, die zum Verlust des parodontalen Attachments führen können. Raucher stellen mit 26 % der Erwachsenen und 12 % der Jugendlichen einen hohen Anteil von Patienten in kieferorthopädischer Behandlung. Wir prüften daher in vivo und in vitro die Hypothese, ob die Applikation kieferorthopädischer Kräfte zu einer Steigerung des nikotininduzierten parodontalen Knochenabbaus führt.

Material und Methoden

Sieben männliche Fischer-344-Ratten erhielten tägliche Injektionen von 1,89 mg L-Nikotin pro kg Körpergewicht s.c., 7 weitere Tiere dienten als Kontrolle. In beiden Gruppen erfolgte eine kieferorthopädische Mesialisation der ersten beiden linken oberen Molaren mittels einer NiTi-Zugfeder, während die kontralaterale Oberkieferseite als Kontrolle diente. Der parodontale Knochenverlust wurde mittels digitaler Volumentomografie (DVT) bestimmt. Humane parodontale Fibroblasten wurden einem Druck von 2 g/cm2 und/oder 3/5/7,5 µM Nikotin ausgesetzt. Bestimmt wurde die Expression von COX-2, PGE2, IL-6, OPG und RANKL auf mRNA- (qRT-PCR) und Proteinebene (ELISA) und quantifiziert wurde die Differenzierung von kokultivierten RAW264.7-Zellen zu osteoklastenähnlichen Zellen mittels TRAP-Färbung.

Ergebnisse

Die kieferorthopädische Kraftapplikation führte in vivo zu einer signifikanten Zunahme des nikotininduzierten parodontalen Knochenverlustes sowie in vitro zu einer Steigerung der Expression von COX-2, PGE2, IL-6 und RANKL, einer Hemmung der OPG-Expression sowie einer vermehrten Differenzierung von osteoklastenähnlichen Zellen aus RAW264.7-Zellen gegenüber der alleinigen Wirkung von Nikotin.

Schlussfolgerungen

Bei der kieferorthopädischen Behandlung von Rauchern ist mit einem vermehrten parodontalen Knochenverlust zu rechnen. Der praktizierende Kieferorthopäde sollte die Patienten über die erhöhten Risiken aufklären, und Zahnbewegungen sollten nur nach Einstellen des Nikotinabusus erfolgen.

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References

  1. Barka T, Anderson PJ (1962) Histochemical methods for acid phosphatase using hexazonium pararosanilin as a coupler. J Histochem Cytochem 10:741–753

    Article  Google Scholar 

  2. Bartal M (2001) Health effects of tobacco use and exposure. Monaldi Arch Chest Dis 56:545–554

    PubMed  Google Scholar 

  3. Bergström J (2004) Tobacco smoking and chronic destructive periodontal disease. Odontology 92:1–8

    Article  PubMed  Google Scholar 

  4. Bosco AF, Bonfante S, Almeida JM de et al (2007) A histologic and histometric assessment of the influence of nicotine on alveolar bone loss in rats. J Periodontol 78:527–532

    Article  PubMed  Google Scholar 

  5. Breivik T, Gundersen Y, Gjermo P et al (2009) Nicotinic acetylcholine receptor activation mediates nicotine-induced enhancement of experimental periodontitis. J Periodontal Res 44:297–304

    Article  PubMed  Google Scholar 

  6. Buttke TM, Proffit WR (1999) Referring adult patients for orthodontic treatment. J Am Dent Assoc 130:73–79

    Article  PubMed  Google Scholar 

  7. Cam GR, Bassett JR (1984) Effect of prolonged exposure to nicotine and stress on the pituitary-adrenocortical response; the possibility of cross-adaptation. Pharmacol Biochem Behav 20:221–226

    Article  PubMed  Google Scholar 

  8. Cattaneo PM, Dalstra M, Melsen B (2009) Strains in periodontal ligament and alveolar bone associated with orthodontic tooth movement analyzed by finite element. Orthod Craniofac Res 12:120–128

    Article  PubMed  Google Scholar 

  9. Chang Y, Tsai C, Yang S et al (2003) Induction of cyclooxygenase-2 mRNA and protein expression in human gingival fibroblasts stimulated with nicotine. J Periodontal Res 38:496–501

    Article  PubMed  Google Scholar 

  10. Cuff MJ, McQuade MJ, Scheidt MJ et al (1989) The presence of nicotine on root surfaces of periodontally diseased teeth in smokers. J Periodontol 60:564–569

    Article  PubMed  Google Scholar 

  11. Dahlberg G (1940) Statistical methods for medical and biological students. G. Allen & Unwin ltd, London

  12. Di Domenico M, D’Apuzzo F, Feola A et al (2012) Cytokines and VEGF induction in orthodontic movement in animal models. J Biomed Biotechnol 2012:201689

    Google Scholar 

  13. ElAttar TM, Lin HS, Tira DE (1981) Effect of epinephrine on prostaglandin E2 and cyclic AMP levels in gingiva of patients with chronic periodontitis. Prostaglandins Med 6:601–612

    Article  PubMed  Google Scholar 

  14. European Commission (2012) Attitudes of Europeans towards tobacco. EUROBAROMETER 77.1 Special Eurobarometer 385. http://ec.europa.eu/health/tobacco/docs/eurobaro_attitudes_towards_tobacco_2012_en.pdf. Accessed 17 Sept 2014

  15. Grudianov AI, Kemulariia IV (2010) Laser Doppler estimation of the influence of tobacco-smoking on the blood microcirculation in the periodont at the patients with the different stages of periodontal diseases. Stomatologiia (Mosk) 89:10–14

  16. Hanes PJ, Schuster GS, Lubas S (1991) Binding, uptake, and release of nicotine by human gingival fibroblasts. J Periodontol 62:147–152

    Article  PubMed  Google Scholar 

  17. Henemyre CL, Scales DK, Hokett SD et al (2003) Nicotine stimulates osteoclast resorption in a porcine marrow cell model. J Periodontol 74:1440–1446

    Article  PubMed  Google Scholar 

  18. Johnson GK, Hill M (2004) Cigarette smoking and the periodontal patient. J Periodontol 75:196–209

    Article  PubMed  Google Scholar 

  19. Kamer AR, El-Ghorab N, Marzec N et al (2006) Nicotine induced proliferation and cytokine release in osteoblastic cells. Int J Mol Med 17:121–127

    PubMed  Google Scholar 

  20. Kanzaki H, Chiba M, Shimizu Y et al (2002) Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis. J Bone Miner Res 17:210–220

    Article  PubMed  Google Scholar 

  21. Kirschneck C, Proff P, Fanghaenel J et al (2013) Differentiated analysis of orthodontic tooth movement in rats with an improved rat model and three-dimensional imaging. Ann Anat 195:539–553

    Article  PubMed  Google Scholar 

  22. Kirschneck C, Wolf M, Reicheneder C et al (2014) Strontium ranelate improved tooth anchorage and reduced root resorption in orthodontic treatment of rats. Eur J Pharmacol 744:67–75

    Article  PubMed  Google Scholar 

  23. Krinke GJ (ed) (2000) The laboratory rat. The handbook of experimental animals. Academic Press, San Diego

  24. Lacey DL, Timms E, Tan HL et al (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176

    Article  PubMed  Google Scholar 

  25. Lampert T, Kuntz B (2014) Tabak- und Alkoholkonsum bei 11- bis 17-jährigen Jugendlichen. Ergebnisse der KiGGS-Studie—Erste Folgebefragung (KiGGS Welle 1). Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 57:830–839

    Article  PubMed  Google Scholar 

  26. Laue E (2010) Nichtraucher auf dem Vormarsch—Gesundheitsschutz hat Vorrang—Statistisches Bundesamt (Destatis). https://www.destatis.de/DE/Publikationen/STATmagazin/Gesundheit/2010_06/2010_06Nichtraucher.html. Accessed 7 Sept 2014

  27. Laxman VK, Annaji S (2008) Tobacco use and its effects on the periodontium and periodontal therapy. J Contemp Dent Pract 9:97–107

    PubMed  Google Scholar 

  28. Lee H, Pi S, Kim Y et al (2009) Effects of nicotine on antioxidant defense enzymes and RANKL expression in human periodontal ligament cells. J Periodontol 80:1281–1288

    Article  PubMed  Google Scholar 

  29. Leone A, Landini L (2013) Vascular pathology from smoking: look at the microcirculation! Curr Vasc Pharmacol 11:524–530

    Article  PubMed  Google Scholar 

  30. Liu Y, Wu L, Wang J et al (2010) Micro-computerized tomography analysis of alveolar bone loss in ligature- and nicotine-induced experimental periodontitis in rats. J Periodontal Res 45:714–719

    Article  PubMed  Google Scholar 

  31. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408

    Article  PubMed  Google Scholar 

  32. Makino A, Yamada S, Okuda K et al (2008) Nicotine involved in periodontal disease through influence on cytokine levels. FEMS Immunol Med Microbiol 52:282–286

    Article  PubMed  Google Scholar 

  33. Malhotra R, Kapoor A, Grover V et al (2010) Nicotine and periodontal tissues. J Indian Soc Periodontol 14:72–79

    Article  PubMed Central  PubMed  Google Scholar 

  34. Meeran NA (2013) Cellular response within the periodontal ligament on application of orthodontic forces. J Indian Soc Periodontol 17:16–20

    Article  PubMed Central  PubMed  Google Scholar 

  35. Meikle MC (2006) The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J Orthod 28:221–240

    Article  PubMed  Google Scholar 

  36. Moore GE, Bross I, Shamberger R et al (1967) Tar and nicotine retrieval from fifty-six brands of cigarettes. Cancer 20:323–332

    Article  PubMed  Google Scholar 

  37. Nakajima R, Yamaguchi M, Kojima T et al (2008) Effects of compression force on fibroblast growth factor-2 and receptor activator of nuclear factor kappa B ligand production by periodontal ligament cells in vitro. J Periodontal Res 43:168–173

    Article  PubMed  Google Scholar 

  38. Nociti FH Jr, Nogueira-Filho GR, Primo MT et al (2000) The influence of nicotine on the bone loss rate in ligature-induced periodontitis. A histometric study in rats. J Periodontol 71:1460–1464

    Article  PubMed  Google Scholar 

  39. Nogueira-Filho, Gda R, Rosa BT, César-Neto JB et al (2007) Low- and high-yield cigarette smoke inhalation potentiates bone loss during ligature-induced periodontitis. J Periodontol 78:730–735

    Article  Google Scholar 

  40. Proff P, Reicheneder C, Faltermeier A et al (2014) Effects of mechanical and bacterial stressors on cytokine and growth-factor expression in periodontal ligament cells. J Orofac Orthop 75:191–202

    Article  PubMed  Google Scholar 

  41. Proff P, Römer P (2009) The molecular mechanism behind bone remodelling: a review. Clin Oral Investig 13:355–362

    Article  PubMed  Google Scholar 

  42. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661

    Article  PubMed  Google Scholar 

  43. Ren Y, Maltha JC, Kuijpers-Jagtman AM (2004) The rat as a model for orthodontic tooth movement – a critical review and a proposed solution. Eur J Orthod 26:483–490

    Article  PubMed  Google Scholar 

  44. Römer P, Köstler J, Koretsi V et al (2013) Endotoxins potentiate COX-2 and RANKL expression in compressed PDL cells. Clin Oral Investig 17:2041–2048

    Article  PubMed  Google Scholar 

  45. Römer P, Wolf M, Fanghänel J et al (2014) Cellular response to orthodontically-induced short-term hypoxia in dental pulp cells. Cell Tissue Res 355:173–180

    Article  PubMed  Google Scholar 

  46. Rose JE, Behm FM, Westman EC et al (1999) Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction. Drug Alcohol Depend 56:99–107

    Article  PubMed  Google Scholar 

  47. Schechter MD, Cook PG (1976) Nicotine-induced weight loss in rats without an effect on appetite. Eur J Pharmacol 38:63–69

    Article  PubMed  Google Scholar 

  48. Sodagar A, Donyavi Z, Arab S et al (2011) Effect of nicotine on orthodontic tooth movement in rats. Am J Orthod Dentofacial Orthop 139:261–265

    Article  Google Scholar 

  49. Takada T, Yoshinari N, Sugiishi S et al (2004) Effect of restraint stress on the progression of experimental periodontitis in rats. J Periodontol 75:306–315

    Article  PubMed  Google Scholar 

  50. Tanaka H, Tanabe N, Shoji M et al (2006) Nicotine and lipopolysaccharide stimulate the formation of osteoclast-like cells by increasing macrophage colony-stimulating factor and prostaglandin E2 production by osteoblasts. Life Sci 78:1733–1740

    Article  PubMed  Google Scholar 

  51. Walpole SC, Prieto-Merino D, Edwards P et al (2012) The weight of nations: an estimation of adult human biomass. BMC Public Health 12:439

    Article  PubMed Central  PubMed  Google Scholar 

  52. Wang X, Liu Y, Wang Q et al (2010) Functional expression of alpha 7 nicotinic acetylcholine receptors in human periodontal ligament fibroblasts and rat periodontal tissues. Cell Tissue Res 340:347–355

    Article  PubMed  Google Scholar 

  53. Wolf M, Lossdörfer S, Craveiro R et al (2013) Regulation of macrophage migration and activity by high-mobility group box 1 protein released from periodontal ligament cells during orthodontically induced periodontal repair: an in vitro and in vivo experimental study. J Orofac Orthop 74:420–434

    Article  PubMed  Google Scholar 

  54. Wu L, Duan D, Liu Y et al (2013) Nicotine favors osteoclastogenesis in human periodontal ligament cells co-cultured with CD4(+) T cells by upregulating IL-1β. Int J Mol Med 31:938–942

    PubMed  Google Scholar 

  55. Xie R, Kuijpers-Jagtman AM, Maltha JC (2011) Inflammatory responses in two commonly used rat models for experimental tooth movement: comparison with ligature-induced periodontitis. Arch Oral Biol 56:159–167

    Article  PubMed  Google Scholar 

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Acknowledgments

We wish to thank Ms. Kathrin Bauer for her technical support in performing the cell experiments.

Danksagung

Die Autoren danken Frau Kathrin Bauer für ihre Unterstützung bei der technischen Durchführung der zellbiologischen Untersuchungen.

Compliance with ethical guidelines

Conflict of interest. C. Kirschneck, P. Proff, M. Maurer, C. Reicheneder, and P. Römer state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

Einhaltung ethischer Richtlinien

Interessenkonflikt. C. Kirschneck, P. Proff, M. Maurer, C. Reicheneder und P. Römer geben an, dass kein Interessenkonflikt besteht.

Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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Authors and Affiliations

  1. Department of Orthodontics, University Medical Center of Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg, Germany

    C. Kirschneck, P. Proff, M. Maurer, C. Reicheneder & P. Römer

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  1. C. Kirschneck
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  2. P. Proff
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  3. M. Maurer
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Correspondence to C. Kirschneck.

Additional information

This work was awarded the 2014 Arnold Biber Prize.

Diese Arbeit ist 2014 mit Arnold-Biber-Preis ausgezeichnet worden.

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Kirschneck, C., Proff, P., Maurer, M. et al. Orthodontic forces add to nicotine-induced loss of periodontal bone. J Orofac Orthop 76, 195–212 (2015). https://doi.org/10.1007/s00056-015-0283-7

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