Contribution of Orthodontic Load to Inflammationmediated Periodontal Destruction

  • Marjan Nokhbehsaim
  • Birgit Deschner
  • Jochen Winter
  • Susanne Reimann
  • Christoph Bourauel
  • Søren Jepsen
  • Andreas Jäger
  • James DeschnerEmail author
Original Article



Orthodontic malpractice as well as hyperocclusal forces can aggravate periodontitis-induced destruction of tooth-supporting tissues, but the underlying mechanisms for the co-destructive effect of biomechanical loading are yet to be elucidated. This in-vitro study was performed to investigate whether biomechanical forces modulate the response of periodontal ligament (PDL) cells to inflammation.

Materials and Methods:

PDL cells (from six donors) grown on BioFlex® plates were treated with interleukin (IL) 1, which is increased at inflamed periodontal sites, and/or subjected to cyclic tensile strain (CTS) of low (3%) and high (20%) magnitudes for 1β and 6 d. The synthesis of proinflammatory mediators (IL1β, IL8, COX2), growth factors (IGF1, VEGF, TGFβ1), collagen type 1 (COL1) and osteogenic proteins (ALP, RUNX2) was analyzed by real-time PCR and ELISA. The wound fill rate was examined in an in-vitro wound healing assay. For statistical analyses, Student’s t-test and ANOVA were applied (p<0.05).


In general, the IL1β-induced expression of proinflammatory mediators was significantly enhanced by CTS on day 1 and significantly downregulated on day 6. CTS of high magnitude significantly inhibited the IGF1 synthesis but significantly upregulated VEGF under normal and inflammatory conditions. In general, CTS also downregulated the IL1β-induced COL1, ALP, and RUNX2 expression. From day 5 on, the lowest wound fill rate was observed in cells which were simultaneously exposed to inflammatory and biomechanical signals.


These findings suggest that orthodontic and occlusal loading may contribute to periodontal destruction in periodontally-diseased patients through downregulation of matrix and osteogenic proteins but not via augmentation of periodontal inflammation.

Key Words:

Orthodontic load Biomechanical forces Inflammation Periodontitis Periodontium PDL cells Cytokines 

Beteiligung von kieferorthopädischer Belastung an der entzündungsvermittelten Destruktion des Parodontiums


Hintergrund und Ziel:

Unsachgemäß durchgeführte kieferorthopädische Zahnbewegungen wie auch okklusale Überbelastungen können eine parodontitisinduzierte Destruktion des Parodontiums verstärken. Die zugrunde liegenden Mechanismen für den destruktionsverstärkenden Effekt der biomechanischen Belastung sind jedoch noch ungeklärt. In dieser In-vitro-Studie sollte untersucht werden, ob biomechanische Kräfte die Reaktion von parodontalen Ligament-(PDL-)Zellen auf Entzündungsreize modulieren.

Material und Methodik:

Auf BioFlex®-Platten kultivierte PDL-Zellen von sechs Patienten wurden mit Interleukin (IL) 1β, das an entzündeten parodontalen Stellen erhöht ist, inkubiert und/oder einer zyklischen Zugbelastung (CTS) niedriger (3%) und hoher (20%) Stärke für 1 und 6 Tage ausgesetzt. Die Synthese von proinflammatorischen Mediatoren (IL1β, IL8, COX2), Wachstumsfaktoren (IGF1, VEGF, TGFβ1), Kollagen Typ 1 (COL1) und osteogenen Proteinen (ALP, RUNX2) wurde mittels Real-Time-PCR und ELISA analysiert. Die Rate der Wundauffüllung wurde mit einem In-vitro-Wundheilungsassay untersucht. Für die statistische Auswertung kamen der Student’s t-Test und ANOVA zur Anwendung (p<0,05).


Im Allgemeinen wurde die IL1β-induzierte Expression der proinflammatorischen Mediatoren durch CTS am Tag 1 signifikant verstärkt und am Tag 6 signifikant gehemmt. CTS hoher Stärke reduzierte signifikant die IGF1-Synthese, führte aber zu einer signifikanten Steigerung von VEGF unter normalen und entzündlichen Bedingungen. CTS hemmte im Allgemeinen auch die IL1β-induzierte Expression von COL1, ALP und RUNX2. Ab dem fünften Tag wurde die geringste Wundheilungsrate in den Kulturen beobachtet, die gleichzeitig entzündlichen und biomechanischen Signalen ausgesetzt waren.


Diese Ergebnisse legen nahe, dass kieferorthopädische und okklusale Kräfte zur parodontalen Destruktion durch Herunterregulation extrazellulärer Matrixproteine und osteogener Differenzierungsmarker, jedoch nicht durch Verstärkung der parodontalen Entzündung bei Parodontitispatienten beitragen könnten.


Kieferorthopädische Belastung Biomechanische Kräfte Entzündung Parodontitis Parodont PDL-Zellen Zytokine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Agarwal S, Long P, Seyedain A, et al. A central role for the nuclear factor-kappaB pathway in anti-inflammatory and proinflammatory actions of mechanical strain. FASEB J 2003;17:899–901.PubMedGoogle Scholar
  2. 2.
    Artun J, Urbye KS. The effect of orthodontic treatment on periodontal bone support in patients with advanced loss of marginal periodontium. Am J Orthod Dentofacial Orthop 1988;93:143–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Balcerzak M, Hamade E, Zhang L, et al. The roles of annexins and alkaline phosphatase in mineralization process. Acta Biochim Pol 2003;50:1019–38.PubMedGoogle Scholar
  4. 4.
    Boyd RL, Baumrind S. Periodontal considerations in the use of bonds or bands on molars in adolescents and adults. Angle Orthod 1992;62:117–26.PubMedGoogle Scholar
  5. 5.
    Chowdhury TT, Akanji OO, Salter DM, et al. Dynamic compression influences interleukin-1beta-induced nitric oxide and prostaglandin E2 release by articular chondrocytes via alterations in iNOS and COX-2 expression. Biorheology 2008;45:257–74.PubMedGoogle Scholar
  6. 6.
    Dereka XE, Markopoulou CE, Vrotsos IA. Role of growth factors on periodontal repair. Growth Factors 2006;24:260–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Deschner J, Rath-Deschner B, Reimann S, et al. Cell biological basics of a motion-based therapy in arthritis — an overview. J Cranio Mand Func 2009;1:107–23.Google Scholar
  8. 8.
    Deschner J, Rath-Deschner B, Reimann S, et al. Regulatory effects of biophysical strain on rat TMJ discs. Ann Anat 2007;189:326–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Fang Y, Svoboda KK. Nicotine inhibits human gingival fibroblast migration via modulation of Rac signalling pathways. J Clin Periodontol 2005;32:1200–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Harrel SK, Nunn ME, Hallmon WW. Is there an association between occlusion and periodontal destruction?: Yes — occlusal forces can contribute to periodontal destruction. J Am Dent Assoc 2006;137:1380,1382,1384 passim.PubMedGoogle Scholar
  11. 11.
    Harrel SK, Nunn ME. The effect of occlusal discrepancies on periodontitis. II. Relationship of occlusal treatment to the progression of periodontal disease. J Periodontol 2001;72:495–505.CrossRefPubMedGoogle Scholar
  12. 12.
    Hoang AM, Oates TW, Cochran DL. In vitro wound healing responses to enamel matrix derivative. J Periodontol 2000;71:1270–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Hou L, Liu C, Chang W. Increased interleukin-1 beta levels in gingival crevicular fluid of Chinese periodontal patients. J Formos Med Assoc 1994;93:99–103.PubMedGoogle Scholar
  14. 14.
    Katz RW, Teng SY, Thomas S, et al. Paracrine activation of extracellular signal-regulated kinase in a simple in vitro model of wounded osteoblasts. Bone 2002;31:288–95.CrossRefPubMedGoogle Scholar
  15. 15.
    Komori T. Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell Tissue Res 2010;339:189–95.CrossRefPubMedGoogle Scholar
  16. 16.
    Lackler KP, Cochran DL, Hoang AM, et al. Development of an in vitro wound healing model for periodontal cells. J Periodontol 2000;71:226–37.CrossRefPubMedGoogle Scholar
  17. 17.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta C(T)) method. Methods 2001;25:402–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Long P, Hu J, Piesco N, et al. 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 2001;80:1416–20.CrossRefPubMedGoogle Scholar
  19. 19.
    Long P, Liu F, Piesco NP, et al. Signaling by mechanical strain involves transcriptional regulation of proinflammatory genes in human periodontal ligament cells in vitro. Bone 2002;30:547–52.CrossRefPubMedGoogle Scholar
  20. 20.
    Okamoto A, Ohnishi T, Bandow K, et al. Reduction of orthodontic tooth movement by experimentally induced periodontal inflammation in mice. Eur J Oral Sci 2009;117:238–47.CrossRefPubMedGoogle Scholar
  21. 21.
    Preiss D, Meyle J. Interleukin-1 beta concentration of gingival crevicular fluid. J Periodontol 1994;65:423–8.PubMedGoogle Scholar
  22. 22.
    Qwarnström EE, MacFarlane SA, Page RC, et al. Interleukin 1 beta induces rapid phosphorylation and redistribution of talin: a possible mechanism for modulation of fibroblast focal adhesion. Proc Natl Acad Sci U S A 1991;88:1232–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Rath-Deschner B, Deschner J, Reimann S, et al. Regulatory effects of biomechanical strain on the IGF system in human periodontal cells. J Biomech 2009;42:2584–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Ren Y, Hazemeijer H, de Haan B, et al. Cytokine profiles in crevicular fluid during orthodontic tooth movement of short and long durations. J Periodontol 2007;78:453–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Ren Y, Vissink A. Cytokines in crevicular fluid and orthodontic tooth movement. Eur J Oral Sci 2008;116:89–97.CrossRefPubMedGoogle Scholar
  26. 26.
    Sabokbar A, Millett PJ, Myer B, et al. A rapid, quantitative assay for measuring alkaline phosphatase activity in osteoblastic cells in vitro. Bone Miner 1994;27:57–67.CrossRefPubMedGoogle Scholar
  27. 27.
    Sallum EJ, Nouer DF, Klein MI, et al. Clinical and microbiologic changes after removal of orthodontic appliances. Am J Orthod Dentofacial Orthop 2004;126:363–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Shimizu N, Yamaguchi M, Goseki T, et al. Cyclic-tension force stimulates interleukin-1 beta production by human periodontal ligament cells. J Periodontal Res 1994;29:328–33.CrossRefPubMedGoogle Scholar
  29. 29.
    Sodek J, McKee MD. Molecular and cellular biology of alveolar bone. Periodontol 2000 2000;24:99–126.CrossRefPubMedGoogle Scholar
  30. 30.
    van Gastel J, Quirynen M, Teughels W, et al. Longitudinal changes in microbiology and clinical periodontal variables after placement of fixed orthodontic appliances. J Periodontol 2008;79:2078–86.CrossRefPubMedGoogle Scholar
  31. 31.
    Wennström JL, Stokland BL, Nyman S, et al. Periodontal tissue response to orthodontic movement of teeth with infrabony pockets. Am J Orthod Dentofacial Orthop 1993;103:313–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Yamamoto T, Kita M, Kimura I, et al. Mechanical stress induces expression of cytokines in human periodontal ligament cells. Oral Dis 2006;12:171–5.CrossRefPubMedGoogle Scholar

Copyright information

© Urban &amp; Vogel, Muenchen 2010

Authors and Affiliations

  • Marjan Nokhbehsaim
    • 1
    • 2
  • Birgit Deschner
    • 1
    • 3
  • Jochen Winter
    • 2
  • Susanne Reimann
    • 4
  • Christoph Bourauel
    • 1
    • 4
  • Søren Jepsen
    • 1
    • 2
  • Andreas Jäger
    • 1
    • 3
  • James Deschner
    • 1
    • 2
    • 5
    Email author
  1. 1.Clinical Research Unit 208Center of Dento-Maxillo-Facial Medicine, University of BonnBonnGermany
  2. 2.Department of PeriodontologyOperative and Preventive Dentistry Center of Dento-Maxillo-Facial Medicine, University of BonnBonnGermany
  3. 3.Department of OrthodonticsCenter of Dento-Maxillo-Facial Medicine, University of BonnBonnGermany
  4. 4.Oral TechnologyCenter of Dento-Maxillo-Facial Medicine, University of BonnBonnGermany
  5. 5.Clinical Research Unit 208Department of Periodontology, Operative and Preventive Dentistry Center of Dento-Maxillo-Facial Medicine University of BonnBonnGermany

Personalised recommendations