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Cyclic Strain Promotes Migration and Proliferation of Human Periodontal Ligament Cell via PI3K Signaling Pathway

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Abstract

Mechanical stimulations have significant impact on cell growth and migration, while little is known on the mechanism of human periodontal ligament cells (hPDLCs) behavior alteration under cyclic strain application. To elucidate the role of PI3K/Akt signaling pathway in cyclic strain-induced migration and proliferation of hPDLCs, 10 or 20%-elongation of cyclic strain at 0.1 Hz-frequency was applied to hPDLCs for 6 h or 24 h with FX-4000T system. The expressions of MMP-13 and p-Akt were examined by Western blotting, and cell proliferation was also detected by BrdU assay. A significant enhance of hPDLCs migration was observed after 24 h of cyclic strain application evaluated with wound healing method, and 20% was found to be more sensitive than 10% of cyclic strain. The strain also significantly increased MMP-13 and p-Akt expressions in hPDLCs as compared with the static. More importantly, the cyclic strain-induced hPDLC migration was suppressed by PI3K/Akt inhibitor wortmannin, and blocked with MMP-13 RNAi pretreatment before loading of 10 or 20%-strain. Additionally, wortmannin suppressed not only the activation of p-Akt, MMP-13 and PCNA, but also the cell proliferation under cyclic strain application in hPDLCs. The findings suggest that cyclic strain promotes the migration and proliferation of hPDLCs by up-regulating the expressions of MMP-13 and PCNA through PI3K/Akt signaling pathway.

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References

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

    Article  Google Scholar 

  2. Archambault, J., M. Tsuzaki, W. Herzog, and A. J. Banes. Stretch and interleukin-1 beta induce matrix metalloproteinases in rabbit tendon cells in vitro. J. Orthop. Res. 20:36–39, 2002.

    Article  Google Scholar 

  3. Danciu, T. E., E. Gagari, R. M. Adam, P. D. Damoulis, and M. R. Freeman. Mechanical strain delivers anti-apoptotic and proliferative signals to gingival fibroblasts. J. Dent. Res. 83:596–601, 2004.

    Article  Google Scholar 

  4. Dimmeler, S., B. Assmus, C. Hermann, J. Haendeler, and A. M. Zeiher. Fluid shear stress stimulates phosphorylation of Akt in human endothelial cells: involvement in suppression of apoptosis. Circ. Res. 83:334–341, 1998.

    Google Scholar 

  5. Doi, H., K. Nishida, M. Yorimitsu, T. Komiyama, Y. Kadota, T. Tetsunaga, A. Yoshida, S. Kubota, M. Takigawa, and T. Ozaki. Interleukin-4 downregulates the cyclic tensile stress-induced matrix metalloproteinases-13 and cathepsin B expression by rat normal chondrocytes. Acta Med. Okayama 62(2):119–126, 2008.

    Google Scholar 

  6. Ferretti, C., L. Bruni, V. Dangles-Marie, A. P. Pecking, and D. Bellet. Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum. Reprod. Update 13:121–141, 2007.

    Article  Google Scholar 

  7. Han, Y., J. S. Pan, D. P. Chen, X. Y. Mao, Y. X. Qi, and Z. Q. Yan. Proliferation of human periodontal ligament cell promoted by cyclic strain via ERK signaling pathway. J. Med. Biomech. 24:211–215, 2009 (in Chinese with English abstract).

    Google Scholar 

  8. Henneman, S., J. W. Von den Hof, and J. C. Maltha. Mechanobiology of tooth movement. Eur. J. Orthod. 30:299–306, 2008.

    Article  Google Scholar 

  9. Horiuchi, M., T. Yamamoto, T. Tomofuji, A. Ishikawa, M. Morita, and T. Watanabe. Toothbrushing promotes gingival fibroblast proliferation more effectively than removal of dental plaque. J. Clin. Periodontol. 29:791–795, 2002.

    Article  Google Scholar 

  10. Ingber, D. E. Mechanobiology and diseases of mechanotransduction. Ann. Med. 35:564–577, 2003.

    Article  Google Scholar 

  11. Kawarizadeh, A., C. Bourauel, W. Götz, and A. Jäger. Early responses of periodontal ligament cells to mechanical stimulus in vivo. J. Dent. Res. 84:902–906, 2005.

    Article  Google Scholar 

  12. Krishnan, V., and Z. Davidovitch. On a path to unfolding the biological mechanisms of orthodontic tooth movement. J. Dent. Res. 88:597–608, 2009.

    Article  Google Scholar 

  13. Leonardia, R., N. F. Talicb, and C. Loretoc. MMP-13 (collagenase 3) immunolocalisation during initial orthodontic tooth movement in rats. Acta Histochem. 109:215–220, 2007.

    Article  Google Scholar 

  14. Malemud, C. J. Matrix metalloproteinases (MMPs) in health and disease: an overview. Front. Biosci. 11:1696–1701, 2006.

    Article  Google Scholar 

  15. Malemud, C. J. Matrix metalloproteinases: role in skeletal development and growth plate disorders. Front. Biosci. 11:1702–1715, 2006.

    Article  Google Scholar 

  16. Manning, B. D., and L. C. Cantley. AKT/PKB signaling: navigating downstream. Cell 129:1261–1274, 2007.

    Article  Google Scholar 

  17. Narayanan, A. S., and R. C. Page. Connective tissues of the periodontium: a summary of current work. Coll. Relat. Res. 3:33–64, 1983.

    Google Scholar 

  18. Pavlin, D., and J. Gluhak-Heinrich. Effect of mechanical loading on periodontal cells. Crit. Rev. Oral Biol. Med. 12:414–424, 2001.

    Article  Google Scholar 

  19. Sato, R., H. Yamamoto, K. Kasai, and M. Yamauchi. Distribution pattern of versican, link protein and hyaluronic acid in the rat periodontal ligament during experimental tooth movement. J. Periodontal. Res. 37:15–22, 2002.

    Article  Google Scholar 

  20. Takahashi, I., M. Nishimura, K. Onodera, J. W. Bae, H. Mitani, M. Okazaki, Y. Sasano, and H. Mitani. Expression of MMP-8 and MMP-13 genes in the periodontal ligament during tooth movement in rats. J. Dent. Res. 82:646–651, 2003.

    Article  Google Scholar 

  21. Tokunaga, E., E. Oki, A. Egashira, N. Sadanaga, M. Morita, Y. Kakeji, and Y. Maehara. Deregulation of the Akt pathway in human cancer. Curr. Cancer Drug Targets 8:27–36, 2008.

    Article  Google Scholar 

  22. Tsurimoto, T. PCNA binding proteins. Front. Biosci. 4:849–858, 1999.

    Article  Google Scholar 

  23. Wang, J. H., and B. P. Thampatty. An introductory review of cell mechanobiology. Biomech. Model. Mechanobiol. 5:1–16, 2006.

    Article  MATH  Google Scholar 

  24. Wescott, D. C., M. N. Pinkerton, B. J. Gaffey, K. T. Beggs, T. J. Milne, and M. C. Meikle. Osteogenic gene expression by human periodontal ligament cells under cyclic tension. J. Dent. Res. 86:1212–1216, 2007.

    Article  Google Scholar 

  25. West, K. A., S. S. Castillo, and P. A. Dennis. Activation of the PI3K/Akt pathway and chemo-therapeutic resistance. Drug Resist. Updat. 5:234–248, 2002.

    Article  Google Scholar 

  26. Wilson, E., K. Sudhir, and H. E. Ives. Mechanical strain of rat vascular smooth muscle cells is sensed by specific extracellular matrix/integrin interactions. J. Clin. Invest. 6:2364–2372, 1995.

    Article  Google Scholar 

  27. Yang, X. Y., and L. Zou. Dual functions of DNA replication forks in checkpoint signaling and PCNA ubiquitination. Cell Cycle 8:191–194, 2009.

    Google Scholar 

  28. Yano, Y., J. Geibel, and B. E. Sumpio. Cyclic strain induces reorganization of integrin alpha 5 beta 1 and alpha 2 beta 1 in human umbilical vein endothelial cells. J. Cell Biochem. 64:505–513, 1997.

    Article  Google Scholar 

  29. Zeichen, J., M. Van Griensven, and U. Bosch. The proliferative response of isolated human tendon fibroblasts to cyclic biaxial mechanical strain. Am. J. Sports Med. 28:888–892, 2000.

    Google Scholar 

  30. Zhou, R. H., T. S. Lee, T. C. Tsou, F. Rannou, Y. S. Li, S. Chien, and J. Y. J. Shyy. Stent implantation activates Akt in the vessel wall: role of mechanical stretch in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 23:2015–2020, 2003.

    Article  Google Scholar 

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Acknowledgments

We would like to thank prof. Zong-Lai Jiang at Institute of Mechanobiology & Medical Engineering, Shanghai Jiao Tong University, China for his valuable suggestions and scientific discussion. This research was supported by grants from the National Natural Science Foundation of China, No. 10502034.

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Correspondence to Jinsong Pan.

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Communicated by Mian Long.

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Han, Y., Pan, J., Wang, X. et al. Cyclic Strain Promotes Migration and Proliferation of Human Periodontal Ligament Cell via PI3K Signaling Pathway. Cel. Mol. Bioeng. 3, 369–375 (2010). https://doi.org/10.1007/s12195-010-0131-1

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  • DOI: https://doi.org/10.1007/s12195-010-0131-1

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