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Purification of prostate-derived bone growth factor and its application to the treatment of osteoporosis

Research Project

Project/Area Number 02557111
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionUaniversity of Tokyo

Principal Investigator

MATSUMOTO Toshio  University of Tokyo, Faculty of Melicine, Lecturer, 医学部(分), 講師 (20157374)

Co-Investigator(Kenkyū-buntansha) OKADA Masahiro  Teijin Institute for Biomedical Research, Lnrestigator, 研究員
IMAIZUMI Atsushi  Teijin Institute for Biomedical Research, chief Inrestigatc, 主任研究員
IKEDA Kyoji  University of Tokyo, Health Service Center, Assistant Professor, 保健センター, 助手 (00222878)
杉山 孝  帝人生物医学研究所, 主任研究員
原田 俊一  東京大学, 医学部, 助手 (70228641)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1990: ¥7,100,000 (Direct Cost: ¥7,100,000)
Keywordsprostate / bone formation / grow factor / osteoporosis / 骨形成因子
Research Abstract

Prostate contains a large amount of various growth factors, and bone metastasis of prostate cancer causes marked osteogenic changes. In an effort to develop a new therapeutic approach to osteoporosis, the present study was undertaken to identify a factor (s) that causes the osteogenic changes and to seek for the application of such a factor to the stimulation of bone formation in patients with osteoporosis.
Urea extract of hypertrophic prostatic tissues obtained at operation or transurethral resection contained both competence and progression growth factor activities, and a strong osteogenic activity was found in the fraction with progression activity. Therefore, the progression activity was purified by a sequencial high performance liquid chromatography using anion exchange, reversed phase, gel filtration, cation exchange, reversed phase, gel filtration heparin affinity, anion excahange and reversed phase columns. Although the progression activity could not be purified to a single band … More on SDS-PAGE, the final fraction of the progression activity had a strong mitogenic activity in osteoblast-like cells. However, the fraction did not stimulate alkaline phosphatase activity in these osteoblastic cells, nor did it enhance ectopic bone formation in vivo when implanted with collagen pellets into subcutaneous tissues in rats. Further analyzes of the osteogenic activity of this factor is neede.
In an effort to identify this factor, peptide mapping was performed after enzymatic digestion of the fraction, and amino acid sequences of digested fragments were determined. Although homologous amino acid sequences with several nuclear proteins such as high mobility group protein-1, cysteine rich protein, histone H1B and H1O were obtained, none of the fagments exhibited homology with any known growth factors, and there were some fragments with unknown amino acid sequences. Because we have human prostatic cDNA library, cDNA cloning of these unknown peptide may reveal a novel prostate-derived osteogenic factor. Less

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Takeuchi, Y. et al: "Effect of transforming growth factor B1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells." Journal of Bone and Mineral Resarch. 8. 821-828 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ishii, T. et al: "Estrogen stimulates the elaboration of cell/matrix surface-associated inhibitory factor of osteo clastic bone resorption from osteoblastic cells." Biochem Biophys Res Commun. 191. 495-502 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsumoto, T. et al: "Matrix proteins regulate the proliferation of osteoblastic cells by ffecting the actions of IGF-I." Osteoporosis Int. 3. 117-120 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okazaki, R. et al: "Transcriptional activation of c-fos and c-jun proto-ancogenes by serum growth factors in osteoblast-like MC3T3-E1 cells." Journal of Bone and Mineral Research. 7. 1149-1155 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hakeda, Y. et al: "Prostaglandin F2α stimulates proliferation of clonal osteoblastic MC3T3-E1 cells by up-regulation of insulin-like growth factor I receptors." Journal of Biological Chemistry. 266. 21044-21050 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Harada, S. et al: "Rale of ascorbic acid in the regulation of proliferation in asteoblast-like MC3T3-E1 cells." Journal of Bone and Mineral Research. 6. 903-908 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Igarashi, C. et al: "Vitamin C and the Scurvy-Prone ODS Rat" Elsevier Science Publishers, 352 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 原田俊一他: "骨代謝調節因子-最近の進歩" 羊士社, 189 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takeuchi Y,Matsumoto T,Ogata E,Shishiba Y.: "Isolation and characterization of proteoglycans synthesized by mouse osteoBlastic cells in culture during the mineralization process." Biochem J. 266 (1). 15-24 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsumoto T,Igarashi C,Takeuchi Y,Harada S,Kikuchi T,Yamamoto H,Ogata E.: "Stimulation by 1,25-dihydroxyvitamin D_31 of in vitro mineralization induced by osteoblast-like MC3T3-E1 cells." Bone. 12 (1). 27-32 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takeuchi Y,Matsumoto T,Ogata E,Shishiba Y.: "Effects of transforming growth factor beta1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells." J Bone Mineral Res. 8 (7). 821-828 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hakeda Y,Harada S,Matsumoto T,Tezuka K,Higashino K,Kodama H,Hashimoto-Goto T,Ogata E,Kumegaya M.: "Prostaglandin F2alpha stimulates proliferation of clonal osteoblastic MC3T3-E1 cells by up-regulation of insulin-like growth factor I receptors." J Biol Chem. 266 (31). 21044-21050 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Harada S,Matsumoto T,Ogata E.: "Role of ascorbic acid in the regulation of proliferation in osteoblast-like MC3T3-E1 cells." J Bone Mineral Res. 6 (9). 903-908 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tukagoshi S,Matsumoto T,Harada S,Ogata E.: "Effect of microfibrillar collagen on growth and differentiation of osteoblast-like MC3T3-E1 cells." J Bone Miner Metab. 10 (1). 26-30 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsumoto T,Harada S,K,awaguchi H,Ogata E.: "Matrix proteins regulate the proliferation of osteoblastic cells by affecting the actions of IGF-I." Osteoprosis Int. 3 (Sup.1). S117-120 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kwaguchi H,Kurokawa T,Hoshino Y,Kawahara H,Ogata E,Matsumoto T.: "Immunohistochemical demonstration of bone morphogenetic protein-2 and transforming growth factor-beta in the ossification of the posterior longitudinal ligament of the cervical spine." Spine. 17 (3S). S33-36 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okazaki R,Ikeda K,Sakamoto A,Nakano T,Morimoto K,Kikuchi T,Urakawa K,Ogata E,Matsumoto T.: "Transcriptional activatio of c-fos and c-jun proto-oncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells." J Bone Mineral Res. 7 (10). 1149-1155 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Matsumoto T,Yamato H,Okazaki R,Kumegawa M,Ogata E.: "Effect of 24,25-dihydroxydroxyvitamin D_3 in osteoclasts." Proc Soc Exp Biol Med. 200 (2). 161-164 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamato H,Okazaki R,Ishii T,Ogata E,Sato T,Kumwgawa M,Akaogi K,Taniguchi N,Matsumoto T.: "Effect of 24R,25-dihydroxyvitamin D_3 on the formation and function of osteoclastic cells." Calcif Tissue Int. 52 (3). 255-260 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ishii T,Saito T,Morimoto K,Takeuchi Y,Asano S,Kumegawa M,Ogata E,Matsumoto T.: "Estrogen stimulates the elaboration of cell/matrix surface-associated inhibitory factor of osteoclastic bone resorption from osteoblastic cells." Biochem Biophys Res Commun. 191 (2). 495-502 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takeuchi,Y.et al: "Isolation and characterization of proteoglycans synthesized by mouse ostecblastic cells in culture during mineralization process." Biochem.Jounal.266. 15-24 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumoto,T,et al: "Stimulation by 1,25-dihydroxyvitamin D_3 of in vitro mineralization induced by osteoblast-like MC3T3-E1 cells." Bone. 12. 27-32 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Harada,S.et al: "Fole of ascorbic acid in the regulation of proliferation in osteoblast-like MC3T3-E1 cells." Jounal of Bone and Mineral Research. 6. 903-908 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hakeda,Y.et al: "Prostagland in F_2α stimulates proliferation of clonal osteoblastic MC3T3-E1 cells by up-regulation of insulin-like growth factor I receptors" Journal of Biological Chemistry. 266. 21044-21050 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kawaguch,H.et al: "Immunohistochemical demonstration of bone morphogenetic protein-2 and transforming growth factor-β in the ossification of the posterior longitudinal ligament of the cervical spine" Spine. 17. 33-36 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsukagoshi,S,et al: "Effect of micro-fibrillar collagen on growth and differentiation of osteoblast-like MC3T3-E1 cells." Journal of Bone and Mineral Metabolism. 10. 26-30 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] lgarashi,C.et al: "Vitamin C and the Scarvy-Prone ODS Rat." Elsevier Science Publishers, 352 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] 原田 俊一 他: "骨代謝調節因子ー最近の進歩" 羊土社, 189 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumoto,T.,et al.: "Stimulation by 1,25-dihydroxyvitamin D_3 of in vitro mineralization indnced by osteoblast-like MC3T3-E1 cells" Bone. 12. 27-32 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Harado,S.,et al.: "Role of ascorbic acid in the regulation of praliferation in osteoblast-like MC3T3-E1 cells" Journal of Bone and Mineral Reseaich. 6. 903-908 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hakeda,Y.,et al.: "Prostaglandin F2d stimulates probferation of clonal osteoblastic MC3T3-E1 cells by up-regulation of insalin-like growth factor I receptors" Journal of Biological Chemistry. 266. 21044-21050 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kawaguchi,H.,et al.: "Immunohisto chemical demonstration of bone morphogenetic protein-α and transforming growth factor-β in the ossification of the postorior longitudinal ligament of the cervical spine" Spine. 17. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsumoto,T.,et al.: "Effect of 24,25-dihydroxyvitamin D_3 in osteoclasts" Proceediys of the Society for Experimental Biology and Medicine. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsumoto,T.,et al.: "Matrix proteins regulate the proliferation of osteoblastic cells by aflecting the aetions of IGF-I" Osteoporosis International. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Igarashi,C.,et al.(分担): "Vitamin C and the scurvy-prone ODS rat" Elsevier Science Publishers B.V., 352 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsumoto,T.,et al.(分担): "Calcium regulation and bone metabolism" Elsevier Science Publishers, 533 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takeuchi,Y,et al.: "Isolation and characterization of proteoglycans synthersized by mouse osteoblastic cells in culture during mineralization process." Biochemical Journal. 266. 15-24 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Fukagawa,M,et al.: "Regression of parathyroid hyperplasia by calcitriolーpulse therapy in patients on longーterm Iialysis" New England Journal of Medicine. 323. 421-422 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Matsumoto,T.et al.: "Stimulation by 1.25ーdihydroxyvitamin D_3 of in vitro mineralization induted by osteoblastーlike MC3T3ーE1 cells." Bone.12. in-press (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Motokura,T.et al.: "Parathyroid hormoneーrelated protein in adult Tーcell leukemia/lymphoma" Annds of Internal Medicine. 111. 484-488 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hakeda,Y.et al.: "Existence of parathyroid hormone binding sites on murine hemopoietic blast cells." Biochemical and Biophysical Research Communications. 163. 1481-1486 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takeuchi,Y.et al.: "1.25ーDihydroxyvitamin D_3 inhibits synthesis and enhancs degradation of proteoglycans in osteoblastic cells." Journal of Biological Chemistry. 264. 18407-18413 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Matsumoto,T.et al.(分担執筆): "Bone Morphometry" Nishimura Co.Niigata,Japan/SmithーGordon & Co.London,UK, 611 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Matsumoto,T.et al.(分担執筆): "Calcium Regulation and Bone Metabolism" Elsevier Science publishers, 508 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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