Journal of Endodontics
Volume 36, Issue 3 , Pages 447-452 , March 2010

Simvastatin Promotes Odontoblastic Differentiation and Expression of Angiogenic Factors via Heme Oxygenase-1 in Primary Cultured Human Dental Pulp Cells

  • Kyung-San Min, DDS, PhD

      Affiliations

    • Department of Conservative Dentistry, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
    • Drs Min and Lee contributed equally to this article.
    • ,
  • Young-Man Lee, MS

      Affiliations

    • Department of Oral and Maxillofacial Pathology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
    • Drs Min and Lee contributed equally to this article.
    • ,
  • Sung-Ok Hong, DDS, MS

      Affiliations

    • Department of Conservative Dentistry, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
    • ,
  • Eun-Cheol Kim, DDS, PhD

      Affiliations

    • Department of Oral and Maxillofacial Pathology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, Republic of Korea
    • Corresponding Author InformationAddress requests for reprints to Dr Eun-Cheol Kim, Department of Oral and Maxillofacial Pathology, School of Dentistry, Wonkwang University, 344-2 Shinyongdong, Iksan, Jeonbuk 579-749, Republic of Korea.

References 

  1. Schröder U. Effects of calcium hydroxide-containing pulp-capping agents on pulp cell migration, proliferation, and differentiation. J Dent Res. 1985;64:541–548
  2. Freeman K, Ludington JR, Svec TA, Pinero GJ, Hoover J. Continuously infused calcium hydroxide: its influence on hard tissue repair. J Endod. 1994;20:272–275
  3. Aeinehchi M, Eslami B, Ghanbariha M, Saffar AS. Mineral troxide aggregate (MTA) and calcium hydroxide as pulp-capping agents in human teeth: a preliminary report. Int Endod J. 2003;36:225–231
  4. Camp JH, Fuks AB. Pediatric endodontics: endodontic treatment for the primary and young permanent. In:  Cohen S,  Burns RC editor. Pathways of the pulp. 9th ed. St Louis, MO: Mosby; 2006;p. 822–882
  5. Six N, Tompkins K, Septier D, Veis A, Goldberg M. Recruitment and characterization of the cells involved in reparative dentin formation in the exposed rat molar pulp after implantation of amelogenin gene splice products A + 4 and A – 4. Oral Biosci Med. 2004;1:35–44
  6. D'Souza RN, Bachman T, Baumgardner KR, Butler WT, Litz M. Characterization of cellular responses involved in reparative dentinogenesis in rat molars. J Dent Res. 1995;74:702–709
  7. Tran-Hung L, Laurent P, Camps J, About I. Quantification of angiogenic growth factors released by human dental cells after injury. Arch Oral Biol. 2008;53:9–13
  8. Iohara K, Zheng L, Wake H, et al. A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp. Stem Cells. 2008;26:2408–2418
  9. Güven G, Altun C, Günhan O, et al. Co-expression of cyclooxygenase-2 and vascular endothelial growth factor in inflamed human pulp: an immunohistochemical study. J.Endod. 2007;33:18–20
  10. Artese L, Rubini C, Ferrero G, Fioroni M, Santinelli A, Piattelli A. Vascular endothelial growth factor (VEGF) expression in healthy and inflamed human dental pulps. J Endod. 2002;28:20–23
  11. d'Aquino R, Graziano A, Sampaolesi M, et al. Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. Cell Death Differ. 2007;14:1162–1171
  12. Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci. 1998;19:26–37
  13. Mundy G, Garrett R, Harris S, et al. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999;286:1946–1949
  14. Maeda T, Matsunuma A, Kawane T, Horiuchi N. Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochem Biophys Res Commun. 2001;280:874–877
  15. Sugiyama M, Kodama T, Konishi K, Abe K, Asami S, Oikawa S. Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Biochem Biophys Res Commun. 2000;271:688–692
  16. Philips BW, Belmonte N, Vernochet C, Ailhaud G, Dani C. Compactin enhances osteogenesis in murine embryonic stems cells. Biochem Biophys Res Commun. 2001;284:478–484
  17. Yazawa H, Zimmermann B, Asami Y, Bernimoulin JP. Simvastatin promotes cell metabolism, proliferation, and osteoblastic differentiation in human periodontal ligament cells. J Periodontol. 2005;76:295–302
  18. Okamoto Y, Sonoyama W, Ono M, et al. Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo. J Endod. 2009;35:367–372
  19. Lin SK, Kok SH, Lee YL, et al. Simvastatin as a novel strategy to alleviate periapical lesions. J Endod. 2009;35:657–662
  20. Otterbein LE, Choi AM. Heme oxygenase: colors of defense against cellular stress. Am J Physiol Lung Cell Mol Physiol. 2000;279:L1029–L1037
  21. Otterbein LE, Soares MP, Yamashita K, Bach FH. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 2003;24:449–455
  22. Min KS, Kwon YY, Lee HJ, et al. Effects of proinflammatory cytokines on the expression of mineralization markers and heme oxygenase-1 in human pulp cells. J Endod. 2006;32:39–43
  23. Lee SK, Min KS, Kim Y, et al. Mechanical stress activates proinflammatory cytokines and antioxidant defense enzymes in human dental pulp cells. J Endod. 2008;34:1364–1369
  24. Kook YA, Lee SK, Son DH, et al. Effects of substance P on osteoblastic differentiation and heme oxygenase-1 in human periodontal ligament cells. Cell Biol Int. 2009;33:424–428
  25. Lee SK, Choi HI, Yang YS, et al. Nitric oxide modulates osteoblastic differentiation with heme oxygenase-1 via the mitogen activated protein kinase and nuclear factor-kappaB pathways in human periodontal ligament cells. Biol Pharm Bull. 2009;32:1328–1334
  26. Grosser N, Hemmerle A, Berndt G, et al. The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells. Free Radic Biol Med. 2004;37:2064–2071
  27. Chen JC, Huang KC, Lin WW. HMG-CoA reductase inhibitors upregulate heme oxygenase-1 expression in murine RAW264.7 macrophages via ERK, p38 MAPK and protein kinase G pathways. Cell Signal. 2006;18:32–39
  28. Hsieh CH, Rau CS, Hsieh MW, et al. Simvastatin-induced heme oxygenase-1 increases apoptosis of Neuro 2A cells in response to glucose deprivation. Toxicol Sci. 2008;101:112–121
  29. Yasuda Y, Ogawa M, Arakawa T, Kadowaki T, Saito T. The effect of mineral trioxide aggregate on the mineralization ability of rat dental pulp cells: an in vitro study. J Endod. 2008;34:1057–1060
  30. Feng JQ, Huang H, Lu Y, et al. The dentine matrix proten 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development. J Dent Res. 2003;82:776–780
  31. Stein GS, Lian JB, Owen TA. Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. FASEB J. 1990;4:3111–3123
  32. Cao G, O'Brien CD, Zhou Z, et al. Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration. Am J Physiol Cell Physiol. 2002;282:C1181–C1190
  33. Lee TS, Tsai HL, Chau LY. Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-Delta 12, 14-prostaglandin J2. J Biol Chem. 2003;278:19325–19330
  34. Nishimoto-Hazuku A, Hirase T, Ide N, Ikeda Y, Node K. Simvastatin stimulates vascular endothelial growth factor production by hypoxia-inducible factor-1alpha upregulation in endothelial cells. J Cardiovasc Pharmacol. 2008;51:267–273
  35. Xu J, Liu X, Chen J, et al. Simvastatin enhances bone marrow stromal cell differentiation into endothelial cells via notch signaling pathway. Am J Physiol Cell Physiol. 2009;296:C535–C543
  36. Ryter SW, Alam J, Choi AM. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev. 2006;86:583–650
  37. Sato K, Balla J, Otterbein L, et al. Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol. 2001;166:4185–4194

PII: S0099-2399(09)01021-8

doi: 10.1016/j.joen.2009.11.021

Journal of Endodontics
Volume 36, Issue 3 , Pages 447-452 , March 2010

Article Tools

* Image Usage & Resolution