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Repair of massive bone defect by bone morphogenetic protein

Research Project

Project/Area Number 04670891
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionOsaka University

Principal Investigator

YOSHIKAWA Hideki  Osaka University Medical School, Assistant Professor, 医学部, 講師 (60191558)

Co-Investigator(Kenkyū-buntansha) UNO Keiro  Osaka University Medical School, Professor, 医学部, 教授 (70028330)
UCHIDA Atsumasa  Osaka University Medical School, Assistant Professor, 医学部, 講師 (40176681)
HASHIMOTO Jun  Osaka University Medical School, Assistant Professor, 医学部, 助手 (40237938)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Keywordsbone morphogenetic protein / osteosarcoma / collagen / bone graft / biomaterial / bone repair
Research Abstract

1. Bone morphogenetic proteins were purified from Dunn osteosarcomas (800g) and human osteosarcomas in nude mice (800g) by guanidine extraction, acetone fractionation, ion-exchange chromatography, gel filtration and HPLC.
2. We tested immunogenicity biocompatibility and biodegrability of various collagens, hydroxyapatites, and biopolymers, in order to select suitable carriers for BMP in vivo.
3. We implanted the composites of BMP and each carrier substance into the back muscles of mice and examined new bone formation radiologically and histologically at 3 weeks.
4. Pepsin-digested bovine skin collagen, hydroxyapatite, polylactic acid, and polylactic acid-polyethelene glycol, block copolymer proved to be suitable carriers for BMP.
5. We implanted the composites of BMP and each carrier substance (collagen, polylactic acid, polylactic acid-polyethelene glycol) beneath the periosteum of rabbit tibia. New bone formation was observed by a composite of BMP/polylactic acid-polyethelene glycol at 4 weeks.
6. We made a bony defect (2cm) in the rabbit tibia and implanted a composite of BMP/polylactic acid-polyethelene glycol in combination with hydroxyapatite rod into the gap of tibia. New bone formation was observed at the surface of the hydroxyapatite rod at 6 weeks and a bony bridge was obtained at 12 weeks.
7. We implanted the composites of BMP and each carrier substance (collagen, polylactic acid, polylactic acid-polyethelene glycol) with and without hydroxyapatite into the back muscles of monkeys. Only BMP/collagen/hydroxyapatite induced new bone formation at 4 weeks.
8. We implanted the composite of BMP/collagen/hydroxyapatite beneath the periosteum of monkey tibia. New bone formation was was observed at 4 weeks.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yoshikawa,H.,et al.: "Immunohistochemical detection of bone morphogenetic proteins in bone and soft-tissue sarcomas." Cancer. 74. 842-847 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa,H.,et al.: "Periosteal sunburst spiculation in osteosarcoma. A possible role for bone morphogenetic protein." Clinical Orthopaedics and Related Research. 308. 213-219 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 吉川秀樹.高岡邦夫: "骨代謝回転と調節因子" 日本臨床. 52. 2262-2267 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyamoto, S., Takaoka, K., Okada, T., Yoshikawa, H., Hashimoto, J., Suzuki, S., Ono, K.: "Evaluation of polylactic acid homopolymers as carriers for bone mophogenetic protein." Clinical Orthopaedic and Related Research. 278. 274-285 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyamoto, S., Takaoka, K., Okada, T., Yoshikawa, H., Hashimoto, J., Suzuki, S., Ono, K.: "Polylactic acid-polyethylene glycol block copolymer : A new biodegradable synthetic carrier for bone morphogenetic protein." Clinical Orthopaedic and Related Research. 294. 333-343 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa, H., Takaoka, K., Hashimoto, J., Masuhara, K., Ono, K.: "Diagnostic and prognostic significance of bone morphogenetic protein in osteosarcoma." Frontiers in Osteosarcoma Research. J.F.Novak, J.H.McMaster (eds.) Hogrefe and Huber. 505-514 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takaoka, K., Yoshikawa, H., Hashimoto, J., Miyamoto, S., Suzuki, S., Matsui, M., Ono, K.: "Purification and characterization of a bone-inducing protein from a murine osteosarcoma." Clinical Orthopaedic and Related Research. 292. 329-336 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takaoka, K., Yoshikawa, H., Hashimoto, J., Masuhara, K., Miyamoto, S., Suzuki, S., Ono, K., Matsui, M., Oikawa, S., Tsuruoka, N., Tawaragi, Y., Inuzuka, C., Katayama, T., Sugiyama, M., Tsujimoto, M., Nakanishi, T., Nakazato, H.: "Gene cloning and expression of a bone morphogenetic protein derived from a murine osteosarcoma (Dunn)." Clinical Orthopaedic and Related Research. 294. 344-352 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hashimoto, J., Takaoka, K., Yoshikawa, H., Miyamoto, S., Suzuki, S., Ono, K.: "A new model of osteopenia using ectopically induced bone : Effects of parathyroid hormone and estradiol on bone turnover in induced bone." Osteoporosis Internatioanl. 3. 128-131 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takaoka, K., Nakagara, H., Yoshikawa, H., Koezuka, M., Hashimoto, J., Miyamoto, S., Suzuki, S., Ono, K.: "Constitution of bone-inducing implants by combining bone morphogenetic protein (BMP) with biomaterials. Experimental studies in mice." Bone Grafts, Derivatives & Substitutes. M.R.Urist, B.T.O 'Conner, and R.G.Burwell (eds.), Butterwort Heinemann. 377-396 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takaoka, K., Yoshikawa, H., Hashimoto, J., Ono, K., Matsui, M., Nakazato, H.: "Transfilter bone induction by Chinese hamster ovary (CHO) cells transfected by DNA encoding bone morphogenetic protein (BMP) -4." Clinical Orthopaedic and Related Research. 300. 269-273 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shimizu, K., Yoshikawa, H., Matsui, M., Masuhara, K., Takaoka, K.: "Periosteal and intratumorous bone formation in atymic nude mice by Chinese hamster ovary tumors expressing murine bone morphogenetic protein-4." Clinical Orthopaedic and Related Research. 300. 274-280 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa, H., Rettin, W.J., Takaoka, K., Alderman, E., Rup, B., Rosen, V., Wozney, J.M., Lane, J.M., Huvos, A.G., Garin-Chesa, P.: "Expression of bone morphogenetic proteins in human osteosarcoma : Immunohistochemical detection with monoclonal antibody." Cancer. 73. 85-91 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakase, T., Nomura, S., Yoshikawa, H., Hashimoto, J., Hirota, S., Kitamura, Y., Oikawa, S., Ono, K., Takaoka, K.: "Transient and localized expression of bone morphogenetic protein 4 messenger RNA during fractrue healing." Jornal of Bone and Mineral Research. 9. 651-659 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa, H., Retting, W.J., Lane, J.M., Takaoka, K., Alderman, E., Rup, B., Rosen, V., Healey, J.H., Huvos, A.G., Garin-Chesa, P.: "Immunohistochemical detection of bone morphogenetic proteins in bone and soft-tissue sarcomas." Cancer. 74. 842-847 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa, H., Shimizu, K., Nakase, T., Takaoka, K. : Periosteal "sunburst spiculation in osteosarcoma: "A possible role for bone morphogenetic protein" Clinical Orthopaedic and Related Research. 308. 213-219 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshikawa,H.,et al.: "Immunohistochemical detecton of bone morphogenetic proteins in bone and soft-tissue sarcomas." Cancer. 74. 842-847 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshikawa,H.,et al.: "Periosteal sunburst spiculation in osteosarcoma.A possible role for bone morphogenetic protein." Clinical Orthopaedics and Related Research. 308. 213-219 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 吉川秀樹.高岡邦夫: "骨代謝回転と調節因子" 日本臨床. 52. 2262-2267 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshikawa,H.et.al.: "Expression of Bone Morphogenetic Proteins in Human Osteosarvoma" Cancer. 73. 85-91 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 吉川秀樹,高岡邦夫: "骨りモデリングにおける骨芽細胞の役割" 医学のあゆみ. 165. 568-571 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 吉川 秀樹 高岡 邦夫: "骨疾患におけるBMPの関与" 実験医学. 10. 2010-2013 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 吉川 秀樹 高岡 邦夫: "骨形成因子-その臨床応用に向けて-" Medical Practice.

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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