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Insulin-like growth factor-II regulates bone sialoprotein gene transcription

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Abstract

Insulin-like growth factor-I and -II (IGF-I and IGF-II) have been found in bone extracts of several different species, and IGF-II is the most abundant growth factor stored in bone. Bone sialoprotein (BSP) is a noncollagenous extracellular matrix glycoprotein associated with mineralized connective tissues. In this study, we have investigated the regulation of BSP transcription by IGF-II in rat osteoblast-like ROS17/2.8 cells. IGF-II (50 ng/ml) increased BSP mRNA and protein levels after 6-h stimulation, and enhanced luciferase activities of the constructs pLUC3 (−116 to +60), pLUC4 (−425 to +60), pLUC5 (−801 to +60) and pLUC6 (−938 to +60). Effects of IGF-II were inhibited by tyrosine kinase, extracellular signal-regulated kinase1/2 and phosphatidylinositol 3-kinase inhibitors, and abrogated by 2-bp mutations in cAMP response element (CRE), FGF2 response element (FRE) and homeodomain protein-binding site (HOX). The results of gel shift assays showed that nuclear proteins binding to CRE, FRE and HOX sites were increased by IGF-II (50 ng/ml) at 3 and 6 h. CREB1, phospho-CREB1, c-Fos and c-Jun antibodies disrupted the formation of the CRE–protein complexes. Dlx5 and Runx2 antibodies disrupted the FRE– and HOX–protein complex formations. These studies therefore demonstrated that IGF-II increased BSP transcription by targeting CRE, FRE and HOX elements in the proximal promoter of the rat BSP gene. Moreover, phospho-CREB1, c-Fos, c-Jun, Dlx5 and Runx2 transcription factors appear to be key regulators of IGF-II effects on BSP transcription.

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References

  1. Jia D, Heersche JNM. Insulin-like growth factor-1 and -2 stimulate osteoprogenitor proliferation and differentiation and adipocyte formation in cell populations derived from adult rat bone. Bone. 2000;27:785–94.

    Article  PubMed  Google Scholar 

  2. Denley A, Cosgrove JC, Booker GW, Wallace JC, Forbes BE. Molecular interactions of the IGF system. Cytokine Growth Factor. 2005;16:421–39.

    Article  Google Scholar 

  3. Oliver MH, Harding JE, Breier BH, Evans PC, Gallaher BW, Gluckman PD. The effects of ovine placental lactogen infusion on metabolites, insulin-like growth factors and binding proteins in the fetal sheep. J Endocrinol. 1995;144:333–6.

    Article  PubMed  Google Scholar 

  4. Rooman R, Koster G, Bloemen R, Gresnigt R, van Buul-Offers SC. The effect of dexamethasone on body and organ growth of normal and IGF-II-transgenic mice. J Endocrinol. 1999;163:543–52.

    Article  PubMed  Google Scholar 

  5. Kang H, Sung J, Jung HM, Woo KM, Hong SD, Roh S. Insulin-like growth factor 2 promotes osteogenic cell differentiation in the parthenogenetic murine embryonic stem cells. Tissue Eng Part A. 2012;18:331–41.

    Article  PubMed  Google Scholar 

  6. Chen L, Jiang W, Huang J, He BC, Zuo GW, Zhang W, Luo Q, Shi Q, Zhang BQ, Wagner ER, Luo J, Tang M, Wietholt C, Luo X, Bi Y, Su Y, Liu B, Kim SH, He CJ, Hu Y, Shen J, Rastegar F, Huang E, Gao Y, Gao JL, Zhou JZ, Reid RR, Luu HH, Haydon RC, He TC, Deng ZL. Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation. J Bone Miner Res. 2010;25:2447–59.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lauzon MA, Daviau A, Drevelle O, Marcos B, Faucheux N. Identification of a growth factor mimicking the synergistic effect of fetal bovine serum on BMP-9 cell response. Tissue Eng Part A. 2014;20:2524–35.

    Article  PubMed  Google Scholar 

  8. Kveiborg M, Flybjerg A, Eriksen EF, Kassem M. Transforming growth factor-beta l stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors. J Endocrinol. 2001;169:549–61.

    Article  PubMed  Google Scholar 

  9. Zhang X, Sobue T, Hurlev MM. FGF-2 increases colony formation, PTH receptor, and IGF-I mRNA in mouse marrow stromal cells. Biochem Biphys Res Commum. 2002;290:526–31.

    Article  Google Scholar 

  10. Zhang K, Chen J, Wang C, Li G, Zheng Z, Zhao R. The expression insulin-like growth factor-I mRNA and polypeptide in rat osteoblast with exposure to parathyroid hormone. Chin Med J. 2003;116:1916–22.

    PubMed  Google Scholar 

  11. Ji C, Chang W, Centrella M, McCarthy TL. Activation domains of CCAAT enhancer binding protein delta: regions required for native activity and prostaglandin E2-dependent transactivation of insulin-like growth factor-I gene expression in rat osteoblasts. Mol Endocrinol. 2003;17:1834–43.

    Article  PubMed  Google Scholar 

  12. Giustina A, Mazziotti G, Canalis E. Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev. 2008;29:535–59.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Denger S, Bähr-Ivacevic T, Brand H, Reid G, Blake J, Seifert M, Lin CY, May K, Benes V, Liu ET, Gannon F. Transcriptome profiling of estrogen-regulated genes in human primary osteoblasts reveals an osteoblast-specific regulation of the insulin-like growth factor binding protein 4 gene. Mol Endocrinol. 2008;22:361–79.

    Article  PubMed  Google Scholar 

  14. Durant D, Pereira RM, Canalis E. Overexpression of insulin-like growth factor binding protein-5 decreases osteoblastic function in vitro. Bone. 2004;35:1256–62.

    Article  PubMed  Google Scholar 

  15. Gregory CW, DeGeorges A, Sikes RA. The IGF axis in the development and progression of prostate cancer. Recent research developments in cancer. Trivandrum: Transworld research network; 2001. p 437–462. ISBN 81-7895-002-2.

  16. Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16:3–34.

    PubMed  Google Scholar 

  17. LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev. 1995;1995(16):143–63.

    Article  Google Scholar 

  18. Parson G, Robinson F, Gibson TB, Xu BE, Karandikar M, Berman K, Cobb MH. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22:153–83.

    Google Scholar 

  19. Osyczka AM, Leboy PS. Bone morphogenetic protein regulation of early osteoblast genes in human marrow stromal cells is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. Endocrinology. 2005;146:3428–37.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mori K, Blanchard F, Charrier C, Battaglia S, Ando K, Duplomb L, Shultz LD, Redini F, Heymann D. Conditioned media from mouse osteosarcoma cells promote MC3T3-E1 cell proliferation using JAKs and PI3-K/Akt signal crosstalk. Cancer Sci. 2008;99:2170–6.

    Article  PubMed  Google Scholar 

  21. Ganss B, Kim RH, Sodek J. Bone sialoprotein. Crit Rev Oral Biol Med. 1999;10:79–98.

    Article  PubMed  Google Scholar 

  22. Ogata Y. Bone sialoprotein and its transcriptional regulatory mechanism. J Perio Res. 2008;43:127–35.

    Article  Google Scholar 

  23. Chen J, Shapiro HS, Sodek J. Developmental expression of bone sialoprotein mRNA in rat mineralized connective tissues. J Bone Miner Res. 1992;7:987–97.

    Article  PubMed  Google Scholar 

  24. Bianco P, Fisher LW, Young MF, Termine JD, Robey PG. Expression of bone sialoprotein (BSP) in developing human tissues. Calcif Tissue Int. 1991;49:421–6.

    Article  PubMed  Google Scholar 

  25. Waltregny D, Bellahcène A, Leval XD, Florkin B, Weidle U, Castronovo V. Increased expression of bone sialoprotein in bone metastases compared with visceral metastases in human breast and prostate cancers. J Bone Miner Res. 2000;15:834–43.

    Article  PubMed  Google Scholar 

  26. Li JJ, Sodek J. Cloning and characterization of the rat bone sialoprotein gene promoter. Biochem J. 1993;289:625–9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kim RH, Shapiro HS, Li JJ, Wrana JL, Sodek J. Characterization of the human bone sialoprotein (BSP) gene and its promoter sequence. Matrix Biol. 1994;14:31–40.

    Article  PubMed  Google Scholar 

  28. Benson MD, Aubin JE, Xiao G, Thomas PE, Franceschi RT. Cloning of a 2.5 kb murine bone sialoprotein promoter fragment and functional analysis of putative Osf2 binding sites. J Bone Miner Res. 1999;14:396–405.

    Article  PubMed  Google Scholar 

  29. Kiyoshima T, Yamauchi M, Wong C, Jheon A, Ganss B, Sodek J. An L1 element disrupts human bone sialoprotein promoter: lack of tissue-specific regulation by distalless5 (Dlx5) and runt homeodomain protein 2 (Runx2)/core binding factor a1 (Cbfa1) elements. Gene. 2002;299:205–17.

    Article  PubMed  Google Scholar 

  30. Li JJ, Kim RH, Sodek J. An inverted TATA box directs downstream transcription of the bone sialoprotein gene. Biochem J. 1995;310:33–40.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kim RH, Sodek J. Transcription of the bone sialoprotein gene is stimulated by v-Src acting through an inverted CCAAT box. Cancer Res. 1999;59:565–71.

    PubMed  Google Scholar 

  32. Shimizu E, Ogata Y. Activation of bone sialoprotein gene transcription by flavonoids is mediated through an inverted CCAAT box in ROS 17/2.8 cells. J Cell Biochem. 2002;86:35–44.

    Article  PubMed  Google Scholar 

  33. Samoto H, Shimizu E, Matsuda-Honjyo Y, Saito R, Nakao S, Yamazaki M, Furuyama S, Sugiya H, Sodek J, Ogata Y. Prostaglandin E2 stimulates bone sialoprotein (BSP) expression through cAMP and fibroblast growth factor 2 response elements in the proximal promoter of the rat BSP gene. J Biol Chem. 2003;278:28659–67.

    Article  PubMed  Google Scholar 

  34. Shimizu-Sasaki E, Yamazaki M, Furuyama S, Sugiya H, Sodek J, Ogata Y. Identification of a novel response element in the rat bone sialoprotein (BSP) gene promoter that mediates constitutive and fibroblast growth factor 2-induced expression of BSP. J Biol Chem. 2001;276:5459–66.

    Article  PubMed  Google Scholar 

  35. Nakayama Y, Nakajima Y, Kato N, Takai H, Kim D, Arai M, Mezawa M, Araki S, Sodek J, Ogata Y. Insulin-like growth factor-I increases bone sialoprotein (BSP) expression through fibroblast growth factor-2 response element and homeodomain protein-binding site in the proximal promoter of the BSP gene. J Cell Physiol. 2006;208:326–35.

    Article  PubMed  Google Scholar 

  36. Ogata Y, Nakao S, Kim RH, Li JJ, Furuyama S, Sugiya H, Sodek J. Parathyroid hormone regulation of bone sialoprotein (BSP) gene transcription is mediated through a pituitary specific transcription factor-1 (Pit-1) motif in the rat BSP gene promoter. Matrix Biol. 2000;2000(19):395–407.

    Article  Google Scholar 

  37. Benson MD, Bargeon JL, Xiao G, Thomas PE, Kim A, Cui Y, Franceschi RT. Identification of a homeodomain binding element in the bone sialoprotein gene promoter that is required for its osteoblast-selective expression. J Biol Chem. 2000;275:13907–17.

    Article  PubMed  Google Scholar 

  38. Ogata Y, Niisato N, Furuyama S, Cheifetz S, Kim RH, Sugiya H. Transforming growth factor-β1 regulation of bone sialoprotein gene transcription: identification of a TGF-β activation element in the rat BSP gene promoter. J Cell Biochem. 1997;65:501–12.

    Article  PubMed  Google Scholar 

  39. Ogata Y, Yamauchi M, Kim RH, Li JJ, Freedman LP, Sodek J. Glucocorticoid regulation of bone sialoprotein (BSP) gene expression: identification of a glucocorticoid response element in the bone sialoprotein gene promoter. Eur J Biochem. 1995;230:183–92.

    Article  PubMed  Google Scholar 

  40. Yamauchi M, Ogata Y, Kim RH, Li JJ, Freedman LP, Sodek J. AP-1 regulation of the rat bone sialoprotein gene transcription is mediated through a TPA response element within a glucocorticoid response unit in the gene promoter. Matrix Biol. 1996;15:119–30.

    Article  PubMed  Google Scholar 

  41. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89:755–64.

    Article  PubMed  Google Scholar 

  42. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108:17–29.

    Article  PubMed  Google Scholar 

  43. Jheon A, Bansal AK, Zhu B, Ganss B, Cheifetz S, Sodek J. Characterisation of the constitutive over-expression of AJ18 in a novel rat stromal bone marrow cell line (D8-SBMC). Arch Oral Biol. 2009;54:705–16.

    Article  PubMed  Google Scholar 

  44. Hamamura K, Zhang P, Yokota H. IGF-Driven PI3 Kinases and TGFβ Signaling Pathways in Chondrogenesis. Cell Biol Int. 2008;32:1238–46.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Kanno T, Takahashi T, Tsujisawa T, Ariyoshi W, Nishihara T. Mechanical stress-mediated Runx2 activation is dependent on Ras/ERK1/2 MAPK signaling in osteoblasts. J Cell Biochem. 2007;101:1266–77.

    Article  PubMed  Google Scholar 

  46. Ge C, Xiao G, Jiang D, Yang Q, Hatch NE, Roca H, Franceschi RT. Identification and functional characterization of ERK/MAPK phosphorylation sites in the Runx2 transcription factor. J Biol Chem. 2009;284:32533–43.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kaliman P, Vinals F, Tester X, Palacin M, Zorzano A. Phosphatidylinositol 3-kinase inhibitors block differentiation of skeletal muscle cells. J Biol Chem. 1996;271:19146–51.

    Article  PubMed  Google Scholar 

  48. Sakaue H, Ogawa W, Matsumoto M, Kuroda S, Takata M, Sugimoto T, Spiegelman BM, Kasuga M. Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase. J Biol Chem. 1998;273:28945–52.

    Article  PubMed  Google Scholar 

  49. Ghosh CN, Abboud SL, Nishimura R, Celeste A, Mahimainathan L, Choudhury GG. Requirement of BMP-2 induced phosphatidylinositol 3-kinase and Akt serine/threonine kinase in osteoblast differentiation and Smad-dependent BMP-2 gene transcription. J Biol Chem. 2002;277:33361–8.

    Article  Google Scholar 

  50. Alberts AS, Arias J, Hagiwara M, Montminy MR, Feeramiso JR. Recombinant cyclic AMP response element binding protein (CREB) phosphorylated on ser-133 is transcriptionally active upon its introduction into fibroblast nuclei. J Biol Chem. 1994;269:7623–30.

    PubMed  Google Scholar 

  51. Chen BP, Liang G, Whelan J, Hai T. ATF3 and ATF3 delta Zip. Transcriptional repression versus activation by alternatively spliced isoforms. J Biol Chem. 1994;269:15819–26.

    PubMed  Google Scholar 

  52. Poli V, Mancini FP, Cortese R. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell. 1990;63:643–53.

    Article  PubMed  Google Scholar 

  53. Sassone-Corsi P. Coupling gene expression to cAMP signalling: role of CREB and CREM. Int J Biochem Cell Biol. 1998;30:27–38.

    Article  PubMed  Google Scholar 

  54. Hassan MQ, Tare RS, Lee SH, Mandeville M, Morasso MI, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB. BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network. J Biol Chem. 2006;281:40515–26.

    Article  PubMed  Google Scholar 

  55. Samee N, de Vernejoul MC, Levi G. Role of DLX regulatory proteins in osteogenesis and chondrogenesis. Crit Rev Eukaryot Gene Expr. 2007;2007(17):173–86.

    Article  Google Scholar 

  56. Wang S, Sasaki Y, Zhou L, Matsumura H, Araki S, Mezawa M, Takai H, Chen Z, Ogata Y. Transcriptional regulation of bone sialoprotein gene by interleukin-11. Gene. 2011;476:46–55.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (Young Scientists (B); 25862057, 25862059, C; No. 25463229), Nihon University President’s Grant for Specified Multidisciplinary Research, and a grant of Strategic Research Base Development Program for Private Universities from Ministry of Education, Culture, Sports, Science, and Technology, Japan (MEXT), 2010-2014 (S1001024).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Periodontology, Nihon University School of Dentistry at Matsudo, Chiba, 271-8587, Japan

    Jin Choe, Yoko Sasaki & Liming Zhou

  2. Anhui Medical University of Stomatology Hospital, Anhui, China

    Liming Zhou

  3. Department of Periodontology and Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo, Chiba, 271-8587, Japan

    Hideki Takai, Yohei Nakayama & Yorimasa Ogata

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  1. Jin Choe
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Correspondence to Yorimasa Ogata.

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Choe, J., Sasaki, Y., Zhou, L. et al. Insulin-like growth factor-II regulates bone sialoprotein gene transcription. Odontology 104, 271–281 (2016). https://doi.org/10.1007/s10266-015-0205-6

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