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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Tunicamycin negatively regulates BMP2-induced osteoblast differentiation through CREBH expression in MC3T3E1 cells

  • Jang, Won-Gu (Dental Science Research Institute and BK21, School of Dentistry, Chonnam National University) ;
  • Kim, Eun-Jung (Dental Science Research Institute and BK21, School of Dentistry, Chonnam National University) ;
  • Koh, Jeong-Tae (Dental Science Research Institute and BK21, School of Dentistry, Chonnam National University)
  • Received : 2011.07.28
  • Accepted : 2011.09.05
  • Published : 2011.11.30
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Abstract

Tunicamycin, an endoplasmic reticulum (ER) stress inducer, specifically inhibits N-glycosylation. The cyclic AMP (cAMP) response element-binding protein H (CREBH) was previously shown to be regulated by UPR-dependent proteolytic cleavage in the liver. On the other hand, the role of CREBH in other tissues is unknown. In the present study, tunicamycin increased the level of CREBH activation (cleavage) as well as mRNA expression in osteoblast cells. Adenoviral (Ad) overexpression of CREBH suppressed BMP2-induced expression of alkaline phosphatase (ALP) and osteocalcin (OC). Interestingly, the BMP2-induced OASIS (structurally similar to CREBH, a positive regulator of osteoblast differentiation) expression was also inhibited by CREBH overexpression. In addition, inhibition of CREBH expression using siRNA reversed the tunicamycin-suppressed ALP and OC expression. These results suggest that CREBH inhibited osteoblast differentiation via suppressing BMP2-induced ALP, OC and OASIS expression in mouse calvarial derived osteoblasts.

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References

  1. Kaufman, R. J. (1999) Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 13, 1211-1233. https://doi.org/10.1101/gad.13.10.1211
  2. Reimertz, C., Kogel, D., Rami, A., Chittenden, T. and Prehn, J. H. (2003) Gene expression during ER stress-induced apoptosis in neurons: induction of the BH3-only protein Bbc3/PUMA and activation of the mitochondrial apoptosis pathway. J. Cell Biol. 162, 587-597. https://doi.org/10.1083/jcb.200305149
  3. Mori, K. (2000) Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 101, 451-454. https://doi.org/10.1016/S0092-8674(00)80855-7
  4. Ron, D. (2002) Translational control in the endoplasmic reticulum stress response. J. Clin. Invest. 110, 1383-1388. https://doi.org/10.1172/JCI0216784
  5. Schroder, M. and Kaufman, R. J. (2005) ER stress and the unfolded protein response. Mutat. Res. 569, 29-63. https://doi.org/10.1016/j.mrfmmm.2004.06.056
  6. Mahoney, W. C. and Duksin, D. (1979) Biological activities of the two major components of tunicamycin. J. Biol. Chem. 254, 6572-6576.
  7. Olden, K., Pratt, R. M., Jaworski, C. and Yamada, K. M. (1979) Evidence for role of glycoprotein carbohydrates in membrane transport: specific inhibition by tunicamycin. Proc. Natl. Acad. Sci. USA 76, 791-795. https://doi.org/10.1073/pnas.76.2.791
  8. Brown, M. S., Ye, J., Rawson, R. B. and Goldstein, J. L. (2000) Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100, 391-398. https://doi.org/10.1016/S0092-8674(00)80675-3
  9. Omori, Y., Imai, J., Watanabe, M., Komatsu, T., Suzuki, Y., Kataoka, K., Watanabe, S., Tanigami, A. and Sugano, S. (2001) CREB-H: a novel mammalian transcription factor belonging to the CREB/ATF family and functioning via the box-B element with a liver-specific expression. Nucleic Acids Res. 29, 2154-2162. https://doi.org/10.1093/nar/29.10.2154
  10. Chin, K. T., Zhou, H. J., Wong, C. M., Lee, J. M., Chan, C. P., Qiang, B. Q., Yuan, J. G., Ng, I. O. and Jin, D. Y. (2005) The liver-enriched transcription factor CREB-H is a growth suppressor protein underexpressed in hepatocellular carcinoma. Nucleic Acids. Res. 33, 1859-1873. https://doi.org/10.1093/nar/gki332
  11. Zhang, K., Shen, X., Wu, J., Sakaki, K., Saunders, T., Rutkowski, D. T., Back, S. H. and Kaufman, R. J. (2006) Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell 124, 587-599. https://doi.org/10.1016/j.cell.2005.11.040
  12. Yamaguchi, A., Komori, T. and Suda, T. (2000) Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr. Rev. 21, 393-411. https://doi.org/10.1210/er.21.4.393
  13. Komori, T. (2006) Regulation of osteoblast differentiation by transcription factors. J. Cell Biochem. 99, 1233-1239. https://doi.org/10.1002/jcb.20958
  14. Wozney, J. M. (1998) The bone morphogenetic protein family: multifunctional cellular regulators in the embryo and adult. Eur. J. Oral. Sci. 106(Suppl 1), 160-166. https://doi.org/10.1111/j.1600-0722.1998.tb02170.x
  15. Canalis, E., Economides, A. N. and Gazzerro, E. (2003) Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr. Rev. 24, 218-235. https://doi.org/10.1210/er.2002-0023
  16. Katagiri, T., Yamaguchi, A., Ikeda, T., Yoshiki, S., Wozney, J. M., Rosen, V., Wang, E. A., Tanaka, H., Omura, S. and Suda, T. (1990) The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. Biochem. Biophys. Res. Commun. 172, 295-299. https://doi.org/10.1016/S0006-291X(05)80208-6
  17. Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T., Rosen, V., Wozney, J. M., Fujisawa-Sehara, A. and Suda, T. (1994) Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J. Cell. Biol. 127, 1755-1766. https://doi.org/10.1083/jcb.127.6.1755
  18. Sakano, S., Murata, Y., Miura, T., Iwata, H., Sato, K., Matsui, N. and Seo, H. (1993) Collagen and alkaline phosphatase gene expression during bone morphogenetic protein (BMP)-induced cartilage and bone differentiation. Clin. Orthop. Relat. Res. 292, 337-344.
  19. Takuwa, Y., Ohse, C., Wang, E. A., Wozney, J. M. and Yamashita, K. (1991) Bone morphogenetic protein-2 stimulates alkaline phosphatase activity and collagen synthesis in cultured osteoblastic cells, MC3T3-E1. Biochem. Biophys. Res. Commun. 174, 96-101. https://doi.org/10.1016/0006-291X(91)90490-X
  20. Ducy, P. and Karsenty, G. (1995) Two distinct osteoblast-specific cis-acting elements control expression of a mouse osteocalcin gene. Mol. Cell. Biol. 15, 1858-1869. https://doi.org/10.1128/MCB.15.4.1858
  21. Saito, A., Ochiai, K., Kondo, S., Tsumagari, K., Murakami, T., Cavener, D. R. and Imaizumi, K. (2011) Endoplasmic reticulum stress response mediated by the PERK-eIF2(alpha)-ATF4 pathway is involved in osteoblast differentiation induced by BMP2. J. Biol. Chem. 286, 4809-4818. https://doi.org/10.1074/jbc.M110.152900
  22. Chen, D., Harris, M. A., Rossini, G., Dunstan, C. R., Dallas, S. L., Feng, J. Q., Mundy, G. R. and Harris, S. E. (1997) Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts. Calcif. Tissue. Int. 60, 283-290. https://doi.org/10.1007/s002239900230
  23. Murakami, T., Saito, A., Hino, S., Kondo, S., Kanemoto, S., Chihara, K., Sekiya, H., Tsumagari, K., Ochiai, K., Yoshinaga, K., Saitoh, M., Nishimura, R., Yoneda, T., Kou, I., Furuichi, T., Ikegawa, S., Ikawa, M., Okabe, M., Wanaka, A. and Imaizumi, K. (2009) Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation. Nat. Cell. Biol. 11, 1205-1211. https://doi.org/10.1038/ncb1963
  24. McInnes, I. B. and Schett, G. (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol. 7, 429-442. https://doi.org/10.1038/nri2094
  25. Firestein, G. S. (2003) Evolving concepts of rheumatoid arthritis. Nature 423, 356-361. https://doi.org/10.1038/nature01661
  26. Kanis, J. A., Borgstrom, F., De Laet, C., Johansson, H., Johnell, O., Jonsson, B., Oden, A., Zethraeus, N., Pfleger, B. and Khaltaev, N. (2005) Assessment of fracture risk. Osteoporos. Int. 16, 581-589. https://doi.org/10.1007/s00198-004-1780-5
  27. Tohmonda, T., Miyauchi, Y., Ghosh, R., Yoda, M., Uchikawa, S., Takito, J., Morioka, H., Nakamura, M., Iwawaki, T., Chiba, K., Toyama, Y., Urano, F. and Horiuchi, K. (2011) The IRE1alpha-XBP1 pathway is essential for osteoblast differentiation through promoting transcription of Osterix. EMBO Rep. 12, 451-457. https://doi.org/10.1038/embor.2011.34
  28. Jang, W. G., Kim, E. J., Bae, I. H., Lee, K. N., Kim, Y. D., Kim, D. K., Kim, S. H., Lee, C. H., Franceschi, R. T., Choi, H. S. and Koh, J. T. (2011) Metformin induces osteoblast differentiation via orphan nuclear receptor SHP-mediated transactivation of Runx2. Bone 48, 885-893. https://doi.org/10.1016/j.bone.2010.12.003
  29. Jang, W. G., Kim, E. J., Lee, K. N., Son, H. J. and Koh, J. T. (2011) AMP-activated protein kinase (AMPK) positively regulates osteoblast differentiation via induction of Dlx5-dependent Runx2 expression in MC3T3E1 cells. Biochem. Biophys. Res. Commun. 404, 1004-1009. https://doi.org/10.1016/j.bbrc.2010.12.099

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