Alterations of Gene Expression by Beta-tricalcium Phosphate in Osteoblast-like MG63 Cells

  • Jeon, Jae-Yun (Division of Oral and Maxillofacial Surgery, Department of Dentistry, College of Medicine, Hanyang University) ;
  • Im, Tae-Yun (Division of Oral and Maxillofacial Surgery, Department of Dentistry, College of Medicine, Hanyang University) ;
  • Jeon, Seung-Hwan (Division of Oral and Maxillofacial Surgery, Department of Dentistry, College of Medicine, Hanyang University) ;
  • Hwang, Kyung-Gyun (Division of Oral and Maxillofacial Surgery, Department of Dentistry, College of Medicine, Hanyang University) ;
  • Park, Chang-Joo (Division of Oral and Maxillofacial Surgery, Department of Dentistry, College of Medicine, Hanyang University)
  • Received : 2011.04.06
  • Accepted : 2011.05.25
  • Published : 2011.07.31

Abstract

Purpose: Beta-tricalcium phosphate (${\beta}$-TCP) is a synthetic calcium phosphate ceramic that has widely been used as a bone material to repair bone defects. Despite many clinical studies, the molecular mechanism whereby this biomaterial alters the gene expression in osteoblasts to promote bone formation is poorly understood. Thus, we attempted to address this question by using microarray techniques to identify the genes that are differentially regulated in osteoblasts exposed to ${\beta}$-TCP. Methods: By using DNA microarrays, we identified several genes whose expression levels were significantly up- or down-regulated in osteoblast-likeMG-63cells cultured with ${\beta}$-TCP at a concentration of 100 mg/10 ml for 24 hours. Results: The differentially expressed genes covered a broad range of functional activities: signal transduction, transcription, cell cycle regulation, vesicular transport, apoptosis, immunity, cytoskeletal elements and cell proliferation and differentiation. Conclusion: The gene expression changes related to cell proliferation and differentiation, vesicle transport, immunity and defense could affect the osteogenic activities of osteoblasts for bone regeneration. However, further studies will be required to verify the relative importance of these genes in bone formation, their temporal and spatial expression patterns and their interactions with each other.

Keywords

References

  1. Trisi P, Rao W, Rebaudi A, Fiore P. Histologic effect of pure- phase beta-tricalcium phosphate on bone regeneration in human artificial jawbone defects. Int J Periodontics Restorative Dent 2003;23:69-77.
  2. Neamat A, Gawish A, Gamal-Eldeen AM. Beta-tricalcium phosphate promotes cell proliferation, osteogenesis and bone regeneration in intrabony defects in dogs. Arch Oral Biol 2009;54:1083-90. https://doi.org/10.1016/j.archoralbio.2009.09.003
  3. Okuda T, Ioku K, Yonezawa I, et al. The effect of the microstructure of beta-tricalcium phosphate on the metabolism of subsequently formed bone tissue. Biomaterials 2007; 28:2612-21. https://doi.org/10.1016/j.biomaterials.2007.01.040
  4. Buser D, Hoffmann B, Bernard JP, Lussi A, Mettler D, Schenk RK. Evaluation of filling materials in membrane-- protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs. Clin Oral Implants Res 1998;9:137-50. https://doi.org/10.1034/j.1600-0501.1998.090301.x
  5. Jensen SS, Broggini N, HjOrting-Hansen E, Schenk R, Buser D. Bone healing and graft resorption of autograft, anorganic bovine bone and beta-tricalcium phosphate. A histologic and histomorphometric study in the mandibles of minipigs. Clin Oral Implants Res 2006;17:237-43. https://doi.org/10.1111/j.1600-0501.2005.01257.x
  6. Kurashina K, Kurita H, Wu Q, Ohtsuka A, Kobayashi H. Ectopic osteogenesis with biphasic ceramics of hydroxyapatite and tricalcium phosphate in rabbits. Biomaterials 2002;23:407-12. https://doi.org/10.1016/S0142-9612(01)00119-3
  7. Merten HA, Wiltfang J, Grohmann U, Hoenig JF. Intraindividual comparative animal study of alpha- and beta- tricalcium phosphate degradation in conjunction with simultaneous insertion of dental implants. J Craniofac Surg 2001;12:59-68. https://doi.org/10.1097/00001665-200101000-00010
  8. Carinci F, Piattelli A, Degidi M, et al. Genetic effects of anorganic bovine bone (Bio-Oss) on osteoblast-like MG63 cells. Arch Oral Biol 2006;51:154-63. https://doi.org/10.1016/j.archoralbio.2005.06.006
  9. Carinci F, Francioso F, Piattelli A, et al. Genetic expression profiling of six odontogenic tumors. J Dent Res 2003;82:551-7. https://doi.org/10.1177/154405910308200713
  10. Carinci F, Pezzetti F, Volinia S, et al. Zirconium oxide: analysis of MG63 osteoblast-like cell response by means of a microarray technology. Biomaterials 2004;25:215-28. https://doi.org/10.1016/S0142-9612(03)00486-1
  11. Liu H, Lu ZG, Miki Y, Yoshida K. Protein kinase C delta induces transcription of the TP53 tumor suppressor gene by controlling death-promoting factor Btf in the apoptotic response to DNA damage. Mol Cell Biol 2007;27:8480-91. https://doi.org/10.1128/MCB.01126-07
  12. Blessing H, Kraus S, Heindl P, Bal W, Hartwig A. Interaction of selenium compounds with zinc finger proteins involved in DNA repair. Eur J Biochem 2004;271:3190-9. https://doi.org/10.1111/j.1432-1033.2004.04251.x
  13. Drabek K, van Ham M, Stepanova T, et al. Role of CLASP2 in microtubule stabilization and the regulation of persistent motility. Curr Biol 2006;16:2259-64. https://doi.org/10.1016/j.cub.2006.09.065
  14. Tsubota A, Matsumoto K, Mogushi K, et al. IQGAP1 and vimentin are key regulator genes in naturally occurring hepatotumorigenesis induced by oxidative stress. Carcinogenesis 2010;31:504-11. https://doi.org/10.1093/carcin/bgp313
  15. West RR, Tenbarge KM, Olmsted JB. A model for microtubule- associated protein 4 structure. Domains defined by comparisons of human, mouse, and bovine sequences. J Biol Chem 1999;266:21886-96.
  16. Matsuguchi T, Chiba N, Bandow K, Kakimoto K, Masuda A, Ohnishi T. JNK activity is essential for Atf4 expression and late-stage osteoblast differentiation. J Bone Miner Res 2009; 24:398-410. https://doi.org/10.1359/jbmr.081107
  17. Sotillo Rodriguez JE, Mansky KC, Jensen ED, et al. Enhanced osteoclastogenesis causes osteopenia in twisted gastrulation- deficient mice through increased BMP signaling. J Bone Miner Res 2009;24:1917-26. https://doi.org/10.1359/jbmr.090507
  18. Fehrenbacher N, Bastholm L, Kirkegaard-SOrensen T, et al. Sensitization to the lysosomal cell death pathway by oncogene- induced down-regulation of lysosome-associated membrane proteins 1 and 2. Cancer Res 2008;68:6623-33. https://doi.org/10.1158/0008-5472.CAN-08-0463
  19. El-Hattab AW, Li FY, Schmitt E, Zhang S, Craigen WJ, Wong LJ. MPV17-associated hepatocerebral mitochondrial DNA depletion syndrome: new patients and novel mutations. Mol Genet Metab 2010;99:300-8. https://doi.org/10.1016/j.ymgme.2009.10.003
  20. Tamura T, Yanai H, Savitsky D, Taniguchi T. The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 2008;26:535-84. https://doi.org/10.1146/annurev.immunol.26.021607.090400
  21. Ishibashi M, Wakita T, Esumi M. 2',5'-Oligoadenylate synthetase- like gene highly induced by hepatitis Cvirus infection in human liver is inhibitory to viral replication in vitro. Biochem Biophys Res Commun 2010;392:397-402. https://doi.org/10.1016/j.bbrc.2010.01.034
  22. Hong L, Chen Z, Zhang X, et al. Zinc ribbon domain containing 1 protein: modulator of multidrug resistance, tumorigenesis and cell cycle. Exp Oncol 2006;28:258-62.
  23. Li WW, Hsiung Y, Zhou Y, Roy B, Lee AS. Induction of the mammalian GRP78/BiP gene by $Ca^{2+}$ depletion and formation of aberrant proteins: activation of the conserved stress-inducible grp core promoter element by the human nuclear factor YY1. Mol Cell Biol 1997;17:54-60. https://doi.org/10.1128/MCB.17.1.54
  24. van Dorst EB, van Muijen GN, Litvinov SV, Fleuren GJ. The limited difference between keratin patterns of squamous cell carcinomas and adenocarcinomas is explicable by both cell lineage and state of differentiation of tumour cells. J Clin Pathol 1998;51:679-84. https://doi.org/10.1136/jcp.51.9.679
  25. Holzinger D, Jorns C, Stertz S, et al. Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling. J Virol 2007;8:7776-85.