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Regeneration of cartilage and bone by transplantation of autologous cells transfected with chondrocyte-inducible genes

Research Project

Project/Area Number 12557156
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Functional basic dentistry
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

KATO Yukio  Hiroshima University Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (10112062)

Co-Investigator(Kenkyū-buntansha) KAWAMOTO Takeshi  Hiroshima University Graduate School of Biomedical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (50224861)
NOSHIRO Mitsuhide  Hiroshima University Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (00144858)
申 鳴  広島大学, 歯学部, 教務員 (20294572)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2002: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2000: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordstranscription / cartilage / mesenchymal stem cells / regeneration / DEC1 / MTF
Research Abstract

We succeeded in regeneration of cartilage and/or bone defects after transplantation of bone marrow mesenchymal stem cells (MSC) in animal models. In addition, forced expression of DEC1 gene in human MSC stimulated chondrocyte differentiation in vitro, DEC1 forced expression suppressed myogenic and adipogenic differentiation and enhanced chondrogenic differentiation. Furthermore, foiled expression of membrane-bound transferrin-like protein (MTF) in mesenchymal cells also enhanced chondrogenic differentiation. Various growth factors and hypoxia stimulated the expression of MTF, DEC1 and/or DEC2 in MSC cultures. These findings suggest that MSC transfected with DEC1, DEC2 or MTF are useful for regeneration medicine.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Honda K., et al.: "The effects of high magnitude cyclic tensile load on cartilage matrix metabolism in cultured chondrocytes"European Journal of Cell Biology. 79. 1-9 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujimoto K., et al.: "Molecular cloning and characterization of DEC2, a new member of basic helix-loop -helix proteins"Biochemical and Biophysisal Research Communications. 280. 164-171 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Teramoto M., et al.: "Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1-stra13-SHARP-2/BHLHB2"Journal of Biochemistry. 129. 391-396 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamasu K., et al.: "Structure and promoter analysis of the mouse membrane-bound transferrin-like protein (MTf) gene"European Journal of Biochemistry. 268. 1468-1476 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida E., et al.: "Direct inhibition of indian hedgehog expression by parathyroid hormone (PTH)/PTH-related peptide and up-regulation by retinoic acid in growth plate chondrocytecultures"Experimental Cell Research. 265. 64-72 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shen M., et al.: "Induction of basic helix-loop-helix protein DEC1(BHLHB2)/Stra13/ Sharp2 in response to the cyclic adenosine monophosphate pathway"European Journal of Cell Biology. 80. 329-334 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koyano Y., et al.: "Chondrocyte-derived ezrin-like domain containing protein (CDEP),a rho guanine nucleotide exchange factor, is inducible in chondrocytes by parathyroid hormone and cyclic AMP and has transforming activity in NIH3T3 Cells"Osteoarthritis and Chartilage. 9,Supplement A. S64-S68 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shen, M., et al.: "Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages"Journal of Biological Chemistry. 277. 50112-50120 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suardita, K., et al.: "Effects of overexpression of membrane-bound transferrin-like protein (MTf) on chondrogenic differentiation in Vitro"Journal of Biological Chemistry. 277. 48579-48586 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyazaki, K., et al.: "Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes"Journal of Biological Chemistry. 277. 47014-47021 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutsumi S., et al.: "Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF"Biochemical and Biophysisal Research Communications. 288. 413-419 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiba H., et al.: "Transforming growth factor-α1 and basic fibroblast growth factor modulate osteocalcin and osteonectin/SPARC syntheses in vitamin-D-activated Pulp cells"Journal of Dental Research. 80. 1653-1659 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honma, S., et al.: "Dec1 and Dec2 are regulators of the mammalian molecular clock"Nature. 419. 841-844 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno, S., et al.: "RGD-CAP(βig-h3) is expressed in precartilage condensation and in prehypertrophic chondrocytes during cartilage development"Biochimica et Biophysica Acta. 1572. 114-122 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno, S., et al.: "RGD-CAP(βig-h3) exerts a negative regulatory function on mineralization in the human periodontal ligament"Journal of Dental Research. 81. 822-825 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno, S., et al.: "Immunohistochemical study of matrilin-1 in arthritic articular cartilage of the mandibular condyle"J. Oral Pathol. Med.. 32. 237-242 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oda, R., et al.: "Effects of Antibodies to Membrane-bound Transferrin-like Protein (MTf) on Cell-shape Change and Chondrocyte Differentiation in the Presence or Absence of Concanavalin"Journal of Cell Science. (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] Makihira, S., et al.: "Thyroid hormone enhances aggrecanase-2/ADAM-TS 5 expression and proteoglycan degradation in growth plate cartilage"Endocrinology. (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] Ikada Y., Editor, Kato Y., et al.: "Tissue Enginearing for Therapeutic Use 5"Excerpta Medica. 226 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 筏義人監修, 加藤幸夫他: "再生医療工学の最先端"(株)シーエムシー出版. 260 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honda K., Ohno S., Tanimoto K., Ijuin C., Tanaka N., Doi T., Kato Y., Tanne K.: "The effects of high magnitude cyclic tensile load on cartilage matrix metabolism in cultured chondrocytes."European Journal of Cell Biology. 79. 1-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujimoto K., Shen M., Noshiro M., Matsybara K., Shingu S., Honda K., Yoshida E., Suardita K., Matsuda Y., and Kato Y.: "Molecelar cloning and characterization of DEC2, a new member of basic helix-loop -helix proteins."Biochemical and Biophysisal Research Communications. 280. 164-171 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Teramoto M., Nakamasu K, Noshiro M., Matsuda Y., Gotoh O. Shen M., Tsutsumi S., Kawamoto T., Iwamoto Y., and Y. Kato.: "Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1-stral3-SHARP-2/BHLHB2."Journal of Biochemistry. 129. 391-396 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshida E. ,Noshiro M., Kawamoto T., Tsutsumi S., Kuruta Y., and Kato Y.: "Direct inhibition of indian hedgehog expression by parathyroid hormone (PTH)/PTH-related peptide and up-regulation by retinoic acid in growth plate chondrocytecultures."Experimental Cell Research. 265. 64-72 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamasu K., Kawamoto T., Yoshida E., Noshiro M., Matsuda Y., and Kato Y.: "Structure and promoter analysis of the mouse membrane-bound transferrin-like protein (MTf) gene."European Journal of Biochemistry. 268. 1468-1476 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shen M., Kawanioto T., Teramoto M., Makihira S., Fujimoto K., Yan W., Noshiro M., and Kato Y.: "Induction of basic helix-loop-helix protein DECI1(BHLHB2)/Stral3/Sharp2 in response to the cyclic adenosine monophosphate pathway."European Journal of Cell Biology. 80. 329-334 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koyano Y., Kawamoto T., Kikuchi A., Shen M., Kuruta Y., Tsutsumi S., Fujimoto K., Noshiro M., Fujii K., and Kato Y.: "Chondrocyte-derived ezrin-like domain containing protein (CDEP), a rho guanine nucleotide exchange factor, is inducible in chondrocytes by parathyroid hormone and cyclic AMP and has transforming activity in NIH3T3 Cells."Osteoarthritis and Chartilage. 9,Supplement A. S64-S68 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutsumi S., Shimazu A., Miyazaki K., Pan H., Koike C., Yoshida E., Takagishi K., and Kato Y.: "Retention of multilineage differentiation potential of njesenchymal cells during proliferation in response to FGF."Biochemical and Biophysisal Research Communications. 288. 413-419 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shiba H., Uchida Y., Kamihagi K., Sakata M., Fujita T., Nakamura S., Takemoto T., Kato Y., and Kurihara H.: "Transforming growth factor-α1 and basic fibroblast growth factor modulate osteocalcin and osteonectin/SPARC syntheses in vitamin-D-activated pulp cells."Journal of Dental Research. 80(7). 1653-1659 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honma, S., Kawamoto, T., Takagi, Y., Fujimoto, K., Sato ,F., Noshiro, M., Kato, Y., Honma, K.: "Dec1 and Dec2 are regulators of the mammalian molecular clock."Nature. 419. 841-844 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno, S., Doi, J., Tsutsumi, S., Okada, Y., Yoneno, K., Kato, Y. and Tanne, K.: "RGD-CAP(βig-h3) is expressed in precartilage condensation and in prehypertrophic chondrocytes during cartilage development."Biochimica et Biophysica Acta. 1572. 114-122 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyazaki, K., Kawamoto, T., Tanimoto, K., Nishiyama, M., Honda, H., and Kato, Y.: "Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes."Journal of Biological Chemistry. 277. 47014-47021 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suardita, K., Fujimoto, K., Oda, R., Shimazu, A., Miyazaki, K., Kawamoto, T., and Kato, Y.: "Effects of overexpression of membrane-bound transferrin like protein (MTf) on chondrogenic differentiation in Vitro."Journal of Biological Chemistry. 277. 48579-48586 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shen, M., Yoshida, E., Yan, W., Kawamoto, T., Suardita, K., Koyano, Y., Fujimoto, K., Noshiro, M., and Kato, Y.: "Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages"Journal of Biological Chemistry. 277. 50112-50120 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno, S., Doi, T., Fujimoto, K., Ijuin, C., Tanaka, N., Tanimoto, K., Honda, K., Nakahara, M., Kato., Y., and Tanne, K.: "RGD-CAP(βig-hS) exerts a negative regulatory function on mineralization in the human periodontal ligament."Journal of Dental Research. 81(12). 822-825 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno, S., Murakami, K., Tanimoto, K., Sugiyama, H., Makihira, S., Shibata, T., Yoneno, K., Kato, Y., Tanne, K.: "Immunohistochemical study of matrilin-1 in arthritic articular cartilage of the mandibular condyle."J. Oral Pathol. Med.. 32. 237-242 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oda, R., Ketut, S., Fujimoto, K., Pan, H., Yan, W., Shimazu, A., Shintani, S., and Kato, Y.: "Effects of Antibodies to Membrane-bound Transferrin-like Protein (MTf) on Cell-shape Change and Chondrocyte Differentiation in the Presence or Absence of Concanavalin."Journal of Cell Science. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Makihira, S., Yan, W., Murakami, H., Furukawa, M., Kawai, T., Nikawa, H., Yoshida, E., Hamada, T., Okada, Y., and Kato, Y.: "Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage."Endocrinology. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shen, M., et al.: "Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages"Journal of Biological Chemistry. 277. 50112-50120 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suardita, K., et al.: "Effects of overexpression of membrane-bound transferrin-like protein (MTf) on chondrogenic differentiation in Vitro"Journal of Biological Chemistry. 277. 48579-48586 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyazaki, K., et al.: "Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes"Journal of Biological Chemistry. 277. 47014-47021 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Honma, S., et al.: "Dec1 and Dec2 are regulators of the mammalian molecular clock"Nature. 419. 841-844 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohno, S., et al.: "RGD-CAP(βig-h3) is expressed in precartilage condensation and in prehypertrophic chondrocytes during cartilage development"Biochimica et Biophysica Acta. 1572. 114-122 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oda, R., et al.: "Effects of Antibodies to Membrane-bound Transferrin-like Protein (MTf) on Cell-shape Change and Chondrocyte Differentiation in the Presence or Absence of Concanavalin"Journal of Cell Science. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Makihira, S., et al.: "Thyroid hormone enhances aggrecanase-2/ADAM-TS5 expression and proteoglycan degradation in growth plate cartilage"Endocrinology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 筏義人監修, 加藤幸夫他: "再生医療工学の最先端"(株)シーエムシー出版. 260 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujimoto K., Shen M., Nishino M., Matsybara K., Shingu S., Honda K., Yoshida E., Suardita K., Matsuda Y., Kato Y: "Molecelar cloning and characterization of DEC2, a new member of basic helix-loop -helix proteins"Biochemical and Biophysisal Research Communications. 280. 164-171 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Teramoto M., Nakamasu K., Noshiro M., Matsuda Y., Gotoh O., Shen M., Tsutsumi S., Kawamoto T., Iwamoto Y., Y.Kato: "Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1-stra13-SHARP-2/BHLHB2"Journal of Biochemistry. 129. 391-396 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshida E., Noshiro M., Kawamoto T., Tsutsumi S., Kuruta T., Kato Y: "Direct inhibition of indian hedgehog expression by parathyroid hormone (PTH)/PTH-related peptide and up-regulation by retinoic acid in growth plate chondrocytecultures"Experimental Cell Research. 265. 64-72 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamasu K., Kawamoto T., Yoshida E., Noshiro M., Matsuda Y., Kato Y.: "Structure and promoter analysis of the mouse membrane-bound transferrin-like protein (MTf) gene."European Journal of Biochemistry. 268. 1468-1476 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shen M., Kawamoto T., Teramoto M., Makihira S., Fuhuniti K., Yan W., Noshiro M, Kato Y.: "Induction of basic helix-loop-helix protein DEC1 (BHLHB2)/Stra13/Sharp2 in response to the cyclic adenosine monophosphate pathway"European Journal of Cell Biology. 80. 329-334 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koyano Y., Kawamoto T., Kikuchi A., Shen M., Kuruta Y., Tsutsumi S., Fujimoto K., Noshiro M., Fujii K., Kato Y.: "Chondrocyte-derived ezrin-like domain containing protein (CDEP), a ★ ★ nucleotide exchange factor, is inducible in chondrocytes by parathyroid hormone and cvclic AMP and has transforming activity in NIH3T3 Cells"Osteoarthritis and Chartilage. 9,Supplement A. S64-S68 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsutsmi S., Shimazu A., Miyasaki K., Pan H., Koike C., Yoshida E., Takagishi K., Kato Y.: "Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF"Biochemical and Biophysisal Research Communications. 288. 413-419 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato Y.: "Tissue Enginearing for Therapeutic Use"(2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Honda K., et al.: "The effects of high magnitude cyclic tensile load on cartilage matrix metabolism in cultured chondrocytes."European Journal of Cell Biology. 79. 1-9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujimoto K., et al.: "Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins."Biochemical and Biophysisal Research Communications. 280. 164-171 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Teramoto M., et al.: "Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1-stra13-SHARP-2/BHLHB2."Journal of Biochemistry. 129. 391-396 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamasu K., et al.: "Structure and promoter analysis of the mouse membrane-bound transferrin-like protein (MTf) gene."European Journal of Biochemistry. 268. 1468-1476 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshida E., et al.: "Direct inhibition of indian hedgehog expression by parathyroid hormone (PTH)/PTH-related peptide and up-regulation by retinoic acid in growth plate chondrocytecultures."Experimental Cell Research. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Kato Y., et al.: "Stimulation of chondrogenic differentiation by a novel transcription factor DEC1 or a cartilage-characteristic membrane protein (MTf)"Tissue Enginearing for Therapeutic Use. (in press).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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