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Induction of IL-6 and MMP-8 in human periodontal fibroblasts by static tensile strain

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Abstract

Objectives

Mechanical loading is a potential activator of inflammation and able to stimulate factors for periodontal and alveolar bone destruction. Aim of this study was to investigate the inflammatory response and synthesis of proteinases by human periodontal ligament fibroblast (HPdLF) dependent on different strengths of static tensile strain (STS).

Materials and methods

HPdLFs were loaded with different STS strengths (1, 5, and 10 %) in vitro. Gene expressions of cyclooxygenase (COX)-2 and interleukin (IL)-6 were analyzed by quantitative real-time polymerase chain reaction. Production of IL-6, prostaglandin E2 (PGE2), matrix metalloproteinase (MMP)-8, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were measured by enzyme-linked immunosorbent assay. Receptor activator of nuclear factor-kappa ligand (RANKL) synthesis was detected by immunocytochemical staining.

Results

Ten percent STS led to an increased gene expression of IL-6 and COX-2 (34.4-fold) in HPdLF, and 1 and 5 % STS slightly reduced the gene expression of IL-6. Synthesis of IL-6 was significantly reduced by 1 % STS and stimulated by 10 % STS. Ten percent STS significantly induced PGE2 production. RANKL was not detectable at any strength of STS. MMP-8 synthesis showed significantly higher values only at 10 % STS, but TIMP-1 was stimulated by 5 and 10 % STS, resulting into highest TIMP-1/MMP-8 ratio at 5 % STS.

Conclusions

High-strength STS is a potent inducer of periodontal inflammation and MMP-8, whereas low-strength STS shows an anti-inflammatory effect. Moderate-strength STS causes the highest TIMP-1/MMP-8 ratio, leading to appropriate conditions for reformation of the extracellular matrix.

Clinical relevance

Furthermore, this study points out that the strength of force plays a pivotal role to achieve orthodontic tooth movement without inducing periodontal inflammation and to activate extracellular matrix regeneration.

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References

  1. Khatib H, Berkovitz D, Ratz T, Plotzki Y, Fainsod A, Gruenbaum Y (1995) Mapping the CdxA gene to a new linkage group in chicken. Anim Genet 26(3):211

    Article  PubMed  Google Scholar 

  2. Belibasakis GN, Guggenheim B (2011) Induction of prostaglandin E(2) and interleukin-6 in gingival fibroblasts by oral biofilms. FEMS Immunol Med Microbiol 63(3):381–386. doi:10.1111/j.1574-695X.2011.00863.x

    Article  PubMed  Google Scholar 

  3. Liu YC, Lerner UH, Teng YT (2000) (2010) Cytokine responses against periodontal infection: protective and destructive roles. Periodontol 52(1):163–206. doi:10.1111/j.1600-0757.2009.00321.x

    Article  Google Scholar 

  4. Lerner UH (2006) Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis. J Dent Res 85(7):596–607

    Article  PubMed  Google Scholar 

  5. Ren Y, Vissink A (2008) Cytokines in crevicular fluid and orthodontic tooth movement. Eur J Oral Sci 116(2):89–97. doi:10.1111/j.1600-0722.2007.00511.x

    Article  PubMed  Google Scholar 

  6. Saito M, Saito S, Ngan PW, Shanfeld J, Davidovitch Z (1991) Interleukin 1 beta and prostaglandin E are involved in the response of periodontal cells to mechanical stress in vivo and in vitro. Am J Orthod Dentofac Orthop 99(3):226–240

    Article  Google Scholar 

  7. Nakamura K, Sahara N, Deguchi T (2001) Temporal changes in the distribution and number of macrophage-lineage cells in the periodontal membrane of the rat molar in response to experimental tooth movement. Arch Oral Biol 46(7):593–607

    Article  PubMed  Google Scholar 

  8. Diercke K, Kohl A, Lux CJ, Erber R (2012) IL-1beta and compressive forces lead to a significant induction of RANKL-expression in primary human cementoblasts. J Orofac Orthop 73(5):397–412. doi:10.1007/s00056-012-0095-y

    Article  PubMed  Google Scholar 

  9. Kanzaki H, Chiba M, Shimizu Y, Mitani H (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(2):210–220. doi:10.1359/jbmr.2002.17.2.210

    Article  PubMed  Google Scholar 

  10. Li Y, Zheng W, Liu JS, Wang J, Yang P, Li ML, Zhao ZH (2011) Expression of osteoclastogenesis inducers in a tissue model of periodontal ligament under compression. J Dent Res 90(1):115–120. doi:10.1177/0022034510385237

    Article  PubMed  Google Scholar 

  11. Apajalahti S, Sorsa T, Railavo S, Ingman T (2003) The in vivo levels of matrix metalloproteinase-1 and -8 in gingival crevicular fluid during initial orthodontic tooth movement. J Dent Res 82(12):1018–1022

    Article  PubMed  Google Scholar 

  12. Lambert E, Dasse E, Haye B, Petitfrere E (2004) TIMPs as multifacial proteins. Crit Rev Oncol Hematol 49(3):187–198. doi:10.1016/j.critrevonc.2003.09.008

    Article  PubMed  Google Scholar 

  13. Nokhbehsaim M, Deschner B, Winter J, Bourauel C, Jager A, Jepsen S, Deschner J (2012) Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1beta in vitro. Clin Oral Investig 16(1):275–283. doi:10.1007/s00784-010-0505-8

    Article  PubMed  Google Scholar 

  14. Brauchli LM, Senn C, Ball J, Wichelhaus (2011) A Force levels of 23 nickel-titanium open-coil springs in compression testing. Am J Orthod Dentofac Orthop 139(5):601–605. doi:10.1016/j.ajodo.2009.06.033

    Article  Google Scholar 

  15. Rozman J, Mrvar P, Drevensek M, Peclin P (2010) Evaluation of NiTi Superelastic Retraction Coil Springs for orthodontic tooth movement in rats. Biomed Mater Eng 20(6):339–348. doi:10.3233/BME-2010-0647

    PubMed  Google Scholar 

  16. Li Y, Tang L, Duan Y, Ding Y (2010) Upregulation of MMP-13 and TIMP-1 expression in response to mechanical strain in MC3T3-E1 osteoblastic cells. BMC Res Notes 3:309. doi:10.1186/1756-0500-3-309

    Article  PubMed Central  PubMed  Google Scholar 

  17. Saito S, Ngan P, Rosol T, Saito M, Shimizu H, Shinjo N, Shanfeld J, Davidovitch Z (1991) Involvement of PGE synthesis in the effect of intermittent pressure and interleukin-1 beta on bone resorption. J Dent Res 70(1):27–33

    Article  PubMed  Google Scholar 

  18. 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(5):1416–1420

    Article  PubMed  Google Scholar 

  19. Nokhbehsaim M, Deschner B, Winter J, Reimann S, Bourauel C, Jepsen S, Jager A, Deschner J (2010) Contribution of orthodontic load to inflammation-mediated periodontal destruction. J Orofac Orthop 71(6):390–402. doi:10.1007/s00056-010-1031-7

    Article  PubMed  Google Scholar 

  20. Somamoto S, Tabata Y (2013) Effect of ProNectin F derivates on cell attachment and proliferation. Acta Biomater 9(2):5194–5200. doi:10.1016/j.actbio.2012.07.039

    Article  PubMed  Google Scholar 

  21. 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(4):402–408. doi:10.1006/meth.2001.1262

    Article  PubMed  Google Scholar 

  22. Stein SH, Dean IN, Rawal SY, Tipton DA (2010) Statins regulate interleukin-1beta-induced RANKL and osteoprotegerin production by human gingival fibroblasts. J Periodontal Res 46(4):483–490. doi:10.1111/j.1600-0765.2011.01364.x

    Article  Google Scholar 

  23. Diercke K, Kohl A, Lux CJ, Erber R (2011) Strain-dependent up-regulation of ephrin-B2 protein in periodontal ligament fibroblasts contributes to osteogenesis during tooth movement. J Biol Chem 286(43):37651–37664. doi:10.1074/jbc.M110.166900

    Article  PubMed Central  PubMed  Google Scholar 

  24. Yang G, Im HJ, Wang JH (2005) Repetitive mechanical stretching modulates IL-1beta induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts. Gene 363:166–172. doi:10.1016/j.gene.2005.08.0069

    Article  PubMed Central  PubMed  Google Scholar 

  25. Ramirez-Yanez GO, Symons AL (2012) Prostaglandin E2 affects osteoblast biology in a dose-dependent manner: an in vitro study. Arch Oral Biol 57(9):1274–1281. doi:10.1016/j.archoralbio.2012.03.003

    Article  PubMed  Google Scholar 

  26. Nakashima A, Tamura M (2006) Regulation of matrix metalloproteinase-13 and tissue inhibitor of matrix metalloproteinase-1 gene expression by WNT3A and bone morphogenetic protein-2 in osteoblastic differentiation. Front Biosci 11:1667–1678

    Article  PubMed  Google Scholar 

  27. Marchesan JT, Scanlon CS, Soehren S, Matsuo M, Kapila YL (2013) Implications of cultured periodontal ligament cells for the clinical and experimental setting: a review. Arch Oral Biol 56(10):933–943. doi:10.1016/j.archoralbio.2011.03.003

    Article  Google Scholar 

  28. Grant M, Wilson J, Rock P, Chapple I (2012) Induction of cytokines, MMP9, TIMPs, RANKL, and OPG during orthodontic tooth movement. Eur J Orthop. doi:10.1093/ejo/cjs057

    Google Scholar 

  29. Uchida M, Shima M, Shimoaka T, Fujieda A, Obara K, Suzuki H, Nagai Y, Ikeda T, Yamato H, Kawaguchi H (2000) Regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by bone resorptive factors in osteoblastic cells. J Cell Physiol 185(2):207–214. doi:10.1002/1097-4652(200011)

    Article  PubMed  Google Scholar 

  30. Onodera S, Nishihira J, Iwabuchi K, Koyama Y, Yoshida K, Tanaka S, Minami A (2002) Macrophage migration inhibitory factor up-regulates matrix metalloproteinase-9 and -13 in rat osteoblasts. Relevance to intracellular signaling pathways. J Biol Chem 277(10):7865–7874. doi:10.1074/jbc.M106020200

    Article  PubMed  Google Scholar 

  31. 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(5):529–535. doi:10.1093/ejo/cjn127

    Article  PubMed  Google Scholar 

  32. Ingman T, Apajalahti S, Mantyla P, Savolainen P, Sorsa T (2005) Matrix metalloproteinase-1 and -8 in gingival crevicular fluid during orthodontic tooth movement: a pilot study during 1 month of follow-up after fixed appliance activation. Eur J Orthod 27(2):202–207. doi:10.1093/ejo/cjh097

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Jutta Goldschmidt, Ute Zerfass, and Lotte Groothusen for their assistance in the laboratory and Katherine Taylor for orthographic correction of the article.

Conflict of interest

The authors declare that no competing financial interest exists.

Author information

Authors and Affiliations

  1. Department of Orthodontics, University Medical Center, Johannes Gutenberg University Mainz, Augustusplatz 2, 55131, Mainz, Germany

    Collin Jacobs, Sarah Grimm, Elena Krieger & Heinrich Wehrbein

  2. Department of Oral and Maxillofacial Surgery, Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany

    Christian Walter & Thomas Ziebart

  3. Department of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Carl-Neubergstr 1, 30625, Hannover, Germany

    Dan Meila

Authors
  1. Collin Jacobs
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  2. Christian Walter
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  4. Sarah Grimm
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  5. Dan Meila
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Correspondence to Collin Jacobs.

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Jacobs, C., Walter, C., Ziebart, T. et al. Induction of IL-6 and MMP-8 in human periodontal fibroblasts by static tensile strain. Clin Oral Invest 18, 901–908 (2014). https://doi.org/10.1007/s00784-013-1032-1

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  • DOI: https://doi.org/10.1007/s00784-013-1032-1

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