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Analysis of the biological function of the BMP binding factor, DAN, during osteoblast differentiation

Research Project

Project/Area Number 13671555
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionChiba Cancer Center Research Institute

Principal Investigator

NAKAMURA Yohko  Chiba Cancer Center Research Institute, Division of Biochemistry, Research Fellow, 生化学研究部, 研究員 (60260254)

Co-Investigator(Kenkyū-buntansha) ISOGAI Eriko  Chiba Cancer Center Research Institute Division of Biochemistry Research Fellow, 生化学研究部, 研究員 (40300917)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsBMP / neuronal differentiation / neuroblastoma / DAN / p53 family / P27^<KIP1> / osteoblast
Research Abstract

DAN, a putative tumor suppressor, was reported to antagonize BMP in Xenopus Oocyts. We investigated the interaction of DAN with BMP2 during osteoblast differentiation and also in transformed cells. A possibility that DAN could bind BMP2 through the cysteine- rich domain was confirmed by in vitro binding assay. During osteoblastic differentiation of mouse osteoblast MC3T3-E1 cells which were treated with ascorbic acid for 6 days, the activity of alkaline phosphatase (ALP)an osteoblastic differentiation marker, was up-regulated while the level of DAN was increased. The activity of ALP in osteoblasts of primary culture prepared from the DAN knockout mouse was down-regulated compared with wild type mouse. Therefore, it was suggested that DAN is regulated during osteoblast differentiation through the interaction with BMP2.
To examine whether human neuroblastoma-derived cell lines could respond to BMP treatment, we analyzed phosphorylation of Smad1/5 in the presence of BMP2. Phosphorylated fo … More rm of Smad1/5 showed a remarkable increase at 30 min after the addition of BMP2. These observations strongly suggest that BMP signaling cascade exists in human neuroblastoma-derived cell lines. The BMP2-dependent neurite outgrowth was also detectable accompanied with the growth inhibition. We have recently found that p73 , a member of p53 family, transactivates the transcription of DAN. To investigate whether functional interaction between DAN and p53 family members could also be involved in the regulation of the BMP-induced differentiation of neuroblastoma cells, we examined the expression levels of DAN and p53 family members in response to BMP2. BMP2 treatment resulted in a significant down-regulation of DAN, p73 and p53 expression in a time-dependent manner. Furthermore, accumulation of Cdk inhibitor, p27^<KIP1> and reduction of Cdk2 activity were detected in BMP2-treated cells. These results suggest that p27^<KIP1> plays a crucial role in the BMP2- induced growth arrest and neuronal differentiation of neuroblastoma cells. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Shinbo, J., Ozaki, T., Nakamura, Y., et al.: "p73-dependent expression of DAN during cisplatin-induced cell death and osteoblast differentiation"Biochem.Biophys.Res.Commun.. 295. 501-507 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iuchi, T., Namba, H., Nakamura, Y., et al.: "Identification of the small interstitial deletion at chromosome band 1p34-p35 and its association with poor outcome in oligodendroglial tumors"Gene, chromosomes & cancer. 35. 170-175 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohtori, S., Yamamoto, T., Nakamura, Y., et al.: "Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal dorsal horn"Neruoscience. 110. 579-586 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomioka, N., Kobayashi, H., Nkamaura, Y., et al.: "Chromosome that show partial loss or gain in near-diploid tumors coincide with chromosomes that show whole loss or gain in near-triploid tumors : Evidence suggesting the involvement of the same genes in the tumorigenesis of high-and low-risk neuroblastomas"Genes Chromosomes Cancer. 36. 139-150 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, Y., Ozaki, T., et al.: "Accumulation of p27^<KIP1> is associated with BMP2-induced growth arrest and neuronal differentiation of human neuroblastoma-derived cell lines"Biochem.Biophys.Res.Commun.. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shinbo, J., Ozaki, T., Nakagawa, T., Watanabe, K., Nakamura, Y., Yamazaki, M., Moriya, H., Nakagawara, A., and Sakiyama, S.: "p73-dependent expression of DAN during cisplatin-induced cell death and osteoblast differentiation"Biochem. Biophys. Res. Commun.. 295. 501-507 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iuchi, T., Namba, H., Iwadate, Y., Shishikura, T., Kageyama, H., Nakamura, Y., Ohira, M., Yamaura, A., Osato, K., Sakiyama, S. and Nakagawara, A.: "Identification of the small interstitial deletion at chromosome band 1p34-p35 and its association with poor outcome in oligodendroglial tumors"Gene, chromosomes & cancer. 35. 170-175 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohtori, S., Yamamoto, T., Ino, H., Hanaoka, E., Shinbo, J., Ozaki, T., Takada, N., Nakamura, Y., Chiba, T., Nakagawara, A., Sakiyama, S., Sakashita, Y., Takahashi, K., Tanaka, K., Yamagata, M., Yamazaki, M., Shimizu, S. and Moriya, H.: "Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal dorsal horn"Neuroscience. 110. 579-586 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tomioka N, Kobayashi H, Kageyama H, Ohira M, Nakamura Y, Sasaki F, Todo S, Nakagawara A, Kaneko Y: "Chromosomes that show partial loss or gain in near-diploid tumors coincide with chromosomes that show whole loss or gain in near-triploid tumors : Evidence suggesting the involvement of the same genes in the tumorigenesis of high- and low-risk neuroblastomas"Genes Chromosomes Cancer. 36(2). 139-150 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura, Y., Ozaki, T., Koseki, H., Nakagawara, A. and Sakiyama, S.: "Accumulation of p27^<KIP1> is associated with BMP2-induced growth arrest and neuronal differentiation of human neuroblastoma-derived cell lines"Biochem. Biophys. Res. Cornmum.. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shinbo, J., Ozaki, T., Nakamura, Y., et al.: "p73-dependent expression of DAN during cisplatin-induced cell death and osteoblast differentiation"Biochem. Biophys. Res. Commun.. 295. 501-507 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iuchi, T., Namba, H., Nakamura, Y., et al.: "Identification of the small interstitial deletion at chromosome band 1p34-p35 and its association with poor outcome in oligodendroglial tumors"Gene, chromosomes & cancer. 35. 170-175 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohtori, S., Yamamoto, T., Nakamura, Y., et al.: "Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal dorsal horn"Neuroscience. 110. 579-586 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tomioka, N., Kobayashi, H., Nakamura, Y., et al.: "Chromosomes that show partial loss or gain in near-diploid tumors coincide with chromosomes that show whole loss or gain in near-triploid tumors : Evidence suggesting the involvement of the same genes in the tumorigenesis of high-and low-risk neuroblastomas"Genes Chromosomes Cancer. 36. 139-150 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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