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2002 Fiscal Year Final Research Report Summary

Bone Induction by Escherichia Coli-Derived Recombinant Human Bone Morphogenetic Protein Variant

Research Project

Project/Area Number 12470437
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

BESSHO Kazuuhisa  Kyoto University, Oral and Maxillofacial Surgery, Assistant Professor, 医学研究科, 助手 (90229138)

Co-Investigator(Kenkyū-buntansha) IIZUKA Tadahiko  Kyoto University, Oral and Maxillofacial Surgery, Professor, 医学研究科, 教授 (80026921)
Project Period (FY) 2000 – 2002
Keywordsbone morphogenetic protein / cytokine / recombinant / purification / Escherichia Coli / bone induction / gene transfer / bioassay
Research Abstract

At present, several recombinant human bone morphogenetic proteins (rhBMPs) can be produced in mammalian cells, such as Chinese hamster ovary (CHO) cells. If rhBMPs with a high activity could be produced in bacteria, the bacterial expression system is invaluable, as it is possible to produce a large quantity of rhBMPs at low-cost.
We examined the bone-inducing ability of Escherichia coli-derived rhBMP-2 (ErhBMP-2) and compared it with that of CHO cell-derived rhBMP-2 (CrhBMP-2) using bioassays. Quantitative analysis indicated that the activity of ErhBMP-2 was higher than that of CrhBMP-2, so ErhBMP-2 may be useful for inducing bone formation. Furthermore, we evaluated the effects of hyperbaric oxygenation (HBO), fibroblast growth factor-2 (FGF-2) and elcatonin on bone formation by ErhBMP-2. These results showed that each therapy is effective in enhancing osteoinduction.
Then we examined the effectiveness of BMP-2 gene transfer by the viral vector in vivo. Osteoinduction was seen when the viral vector was injected immunosuppression. Therefore, we evaluated osteoinduction by the viral vector using atelopeptide collagen to mask the immune response or local application of immunosappressant in immunocompetent rats
Our results suggested that ErhBMP-2 and gene therapy with the BMP-2-expressing adenoviral vector may be useful for bone reconstruction.

  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2 at Intramuscular, Intermuscular, Subcutaneous and Intrafatty Sites"International Journal of Oral and Maxillofacial Surgery. 29. 62-66 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuzo Konishi, Kazuhisa Bessho, et al.: "Bone Induction by Escherichia Coli-Derived Recombinant Human Bone Morphogenetic Protein-2 Variant with Collagen as a Carrier"Dentistry in Japan. 36. 66-68 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Effect of Elcatonin on Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2"Biochemical and Biophysical Research Communications. 269. 317-321 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhisa Bessho, Yasuzo Konishi, et al.: "Bone Induction by Escherichia Coli-derived Recombinant Human BMP-2 Compared with Chinese Hamster Ovary Cell-derived Recombinant Human BMP-2"British Journal of Oral and Maxillofacial Surgery. 38. 645-649 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Osteogenesis by Recombinant Human Bone Morphogenetic Protein-2 at Skeletal Sites"Clinical Orthopaedics and Related Research. 375. 295-301 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ichiro Kurokawa, Kazuhisa Beshho, et al.: "Immunohistochemical Expression of Bone Morphogenetic Protein-2 in Calcifying Epithelioma"British Journal of Dermatology. 143. 754-758 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kenji Kusumoto, Kazuhisa Bessho, et al.: "The Effect of Blood Supply in Muscle and an Elevated Muscle Flap on Endogenous Tissue Engineered Bone by rhBMP-2 in the Rat"Annals of Plastic Surgery. 45. 408-414 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Effect of Hyperbaric Oxygenation on Induced Bone by Recombinant Human Bone Morphogenetic Protein-2"British Journal of Oral and Maxillofacial Surgery. 39. 91-95 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshikazu Suzuki, Kazuhisa Bessho, et al.: "Immunohistochemical Localization of Bone Morphogenetic Protein-2 in the Oral and Maxillofacial Area of the Human an Embryo"British Journal of Oral and Maxillofacial Surgery. 39. 289-293 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuma Fujimura, Kazuhisa Bessho, et al.: "Experimental Osteoinduction by Recombinant Human Bone Morphogenetic Protein 2 in Tissue with Low-Blood Flow : A Study in Rats"British Journal of Oral and Maxillofacial Surgery. 39. 294-300 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasuhiko Kiyozuka, Kazuhisa Bessho, et al.: "Bone Morphogenetic Protein-2 and Type IV Collagen Expression in Psammoma a Body Forming Ovarian Cancer"Anticancer Research. 21. 1723-1730 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "The Time Course Study of Osteoinduction by Bone Morphogenetic Protein-2 via Adenoviral Vector"Life Science. 70. 325-336 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Expression of Bone Morphogenetic Protein in the Course of Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2"Clinical Oral Implants Research. 13. 80-85 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshikazu Suzuki, Kazuhisa Bessho, et al.: "Regeneration of Defects in the Articular Cartilage in Rabbit Temporomandibular Joints by Bone Morphogenetic Protein-2"British Journal of Oral and Maxillofacial Surgery. 40. 201-206 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhisa Bessho, David L.Carnes, et al.: "Experimental Studies on Bone Induction Using Low Molecular Weight Poly (DL-lactide-co-glycolide) as a Carrier for Recombinant Human Bone Morphogenetic Protein-2"Journal of Biomedical Materials Research. 61. 61-65 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kenji Kusumoto, Kazuhisa Bessho, et al.: "Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2 in Muscles of Non-human Primates"The Journal of International Medical Research. 30. 251-259 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhisa Bessho, Junya Sonobe, et al.: "In Vivo Serial Changes in Bone Induction by E.Coli-derived Recombinant Human Bone Morphogenetic Protein-2"Journal of Musculoskeletal Research. 6. 1-7 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jiro Akioka, Kazuhisa Bessho, et al.: "Angioneogenesis around Induced Bone with Recombinant Human Bone Morphogenetic Protein-2 in a Latissimus Dorsi Muscle Flap"Journal of Musculoskeletal Research. 6. 17-21 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Junya Sonobe, Kazuhisa Bessho, et al.: "Bone Induction by BMP-2 Expressing Adenoviral Vector in Rats under Treatment with FK506"Journal of Musculoskeletal Research. 6. 23-29 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kris Partridge, Kazuhisa Bessho, et al.: "Adenoviral BMP-2 Gene Transfer in Mesenchymal Stem Cells : In Vitro and in Vivo Bone Formation on Biodegradable Polymer Scaffolds"Biochemical and Biophysical Research Communication. 292. 144-152 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuma Fujimura, Kazuhisa Bessho, et al.: "The Effect of Fibroblast Growth Factor-2 on Osteoinducing Activity of Recombinant Human Bone Morphogenetic Protein-2 in Rat Muscle"Archives of Oral Biology. 47. 577-584 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinji Kaihara, Kazuhisa Bessho, et al.: "Effect of FK506 on Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2"Life Science. 72. 247-256 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Daniel Howard, Kazuhisa Bessho, et al.: "Immunoselection and Adenoviral Genetic Modulation of Human Osteoprogenitors : In Vivo Bone Formation on PLA Scaffold"Biochemical and Biophysical Research Communications. 299. 208-215 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinji Kaihara, Kazuhisa Bessho, et al.: "Over Expression of BMP-3b Using an Adenoviral Vector Promote the Osteoblastic Differentiation in C2C12 Cells and Augment the Bone Formation Induced by BMP-2) in Rats"Life Science. 72. 1683-1693 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhisa Bessho, Joo L.Ong, et al.: "Biomaterials and Bioengineering Handbook"Marcel Dekker, Inc.. 920 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kenji Kusumoto, Kazuhisa Bessho: "Current Topics in Biochemical Research, Volume 3"Research Trends. 68 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhisa Bessho, Joo L.Ong: "Advances in Skeletal Reconstruction Using Bone Morphogenetic Proteins"The World Scientific Publishing Company. 456 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazuhisa Bessho: "Recent Research Development in Biophysics & Biochemistry"Research Signpost (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2 at Intramuscular, Inter-muscular, Subcutaneous and Intrafatty Sites"International Journal of Oral and Maxillofacial Surgery. 29. 62-66 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasuzo Konishi, Kazuhisa Bessho, et al.: "Bone Induction by Escherichia Coli-Derived Recombinant Human Bone Morphogenetic Protein-2 Variant with Collagen as a Carrier"Dentistry in Japan. 36. 66-68 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Effect of Elcatonin on Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2"Biochemical and Biophysical Research Communications. 269. 317-321 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuhisa Bessho, Yasuzo Konishi, et al.: "Bone Induction by Escherichia Coli-derived Recombinant Human BMP-2 Compared with Chinese Hamster Ovary Cell-derived Recombinant Human BMP-2"British Journal of Oral and Maxillofacial Surgery. 38. 645-649 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Osteogenesis by Recombinant Human Bone Morphogenetic Protein-2 at Skeletal Sites"Clinical Orthopaedics and Related Research. 375. 295-301 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichiro Kurokawa, Kazuhisa Bessho, et al.: "Immunohistochemical Expression of Bone Morphogenetic Protein-2 in Calcifying Epithelioma"British Journal of Dermatology. 143. 754-758 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji Kusumoto, Kazuhisa Bessho, et al.: "The Effect of Blood Supply in Muscle and an Elevated Muscle Flap on Endogenous Tissue Engineered Bone by rhBMP-2 in the Rat"Annals of Plastic Surgery. 45. 408-414 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Effect of Hyperbaric Oxygenation on Induced Bone by Recombinant Human Bone Morphogenetic Protein-2"British Journal of Oral and Maxillofacial Surgery. 39. 91-95 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toshikazu Suzuki, Kazuhisa Bessho, et al.: "Immunohistochemical Localization of Bone Morphogenetic Protein-2 in the Oral and Maxiliofacial Area of the Human Embryo"British Journal of Oral and Maxillofacial Surgery. 39. 289-293 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuma Fujimura, Kazuhisa Bessho, et al.: "Experimental Osteoinduction by Recombinant Human Bone Morphogenetic Protein 2 in Tissue with Low-Blood Flow: A Study in Rats"British Journal of Oral and Maxillofacial Surgery. 39. 294-300 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasuhiko Kiyozuka, Kazuhisa Bessho, et al.: "Bone Morphogenetic Protein-2 and Type IV Collagen Expression in Psammoma Body Forming Ovarian Cancer"Anticancer Research. 21. 1723-1730 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "The Time Course Study of Osteoinduction by Bone Morphogenetic Protein-2 via Adenoviral Vector"Life Science. 70. 325-336 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasunori Okubo, Kazuhisa Bessho, et al.: "Expression of Bone Morphogenetic Protein in the Course of Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2"Clinical Oral Implants Research. 13. 80-85 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toshikazu Suzuki, Kazuhisa Bessho, et al.: "Regeneration of Defects in the Articular Cartilage in Rabbit Temporomandibular Joints by Bone Morphogenetic Protein-2"British Journal of Oral and Maxillofacial Surgery. 40. 201-206 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuhisa Bessho, David L. Cames, et al.: "Experimental Studies on Bone Induction Using Low Molecular Weight Poly (DL-lactide-co-glycolide) as a Carrier for Recombinant Human Bone Morphogenetic Protein-2"Journal of Biomedical Materials Research. 61. 61-65 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji Kusumoto, Kazuhisa Bessho, et al.: "Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2 in Muscles of Non-human Primates"The Journal of International Medical Research. 30. 251-259 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuhisa Bessho, Junya Sonobe, et al.: "In Vivo Serial Changes in Bone Induction by E. Coli-derived Recombinant Human Bone Morphogenetic Protein-2"Journal of Musculoskeletal Research. 6. 1-7 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jiro Akioka, Kazuhisa Bessho, et al.: "Angioneogenesis around Induced Bone with Recorabinant Human Bone Morphogenetic Protein-2 in a Latissimus Dorsi Muscle Flap"Journal of Musculoskeletal Research. 6. 17-21 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Junya Sonobe, Kazuhisa Bessho, et al.: "Bone Induction by BMP-2 Expressing Adenoviral Vector in Rats under Treatment with FK506"Journal of Musculoskeletal Research. 6. 23-29 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kris Partridge, Kazuhisa Bessho, et al.: "Adenoviral BMP-2 Gene Transfer in Mesenchymal Stem Cells: In Vitro and in Vivo Bone Formation on Biodegradable Polymer Scaffolds"Biochemical and Biophysical Research Communications. 292. 144-152 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuma Fujimura, Kazuhisa Bessho, et al.: "The Effect of Fibroblast Growth Factor-2 on Osteoinducing Activity of Recombinant Human Bone Morphogenetic Protein-2 in Rat Muscle"Archives of Oral Biology. 47. 577-584 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinji Kaihara, Kazuhisa Bessho, et al.: "Effect of FK506 on Osteoinduction by Recombinant Human Bone Morphogenetic Protein-2"Life Science. 72. 247-256 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Daniel Howard, Kazuhisa Bessho, et al.: "Immunoselection and Adenoviral Genetic Modulation of Human Osteoprogenitors: In Vivo Bone Formation on PLA Scaffold"Biochemical and Biophysical Research Communications. 299. 208-215 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinji Kaihara, Kazuhisa Bessho, et al.: "Over Expression of BMP-3b Using an Adenoviral Vector Promote the Osteoblastic Differentiation in C2C12 Cells and Augment the Bone Formation Induced by BMP-2) in Rats"Life Science. 72. 1683-1693 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazubisa Bessho, Tadahiko Iizuka, D. L. Wise ed.: "Bone Morphogenetic Proteins and Biomaterials as Carriers, in Biomaterials and Bioengineering Handbook"Marcel Dekker. 373-382 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji Kusumoto, Kazuhisa Bessho: "Osteoinduction by Bone Morphogenetic Protein (BMP); Basic Aspects in the Application to Tissue Engineering In Current Topics in Biochemical Research, Volume 3"Research Trends. 55-68 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuhisa Bessho, Joo L Ong, T. S. Lindholm ed.: "Effect of BMP around Dental Implant, in: Advances in Skeletal Reconstruction Using Bone Morphogenetic Proteins"The World Scientific Publishing Company. 334-344 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazuhisa Bessho: "Osteoinduction by a Human Bone Morphogenetic Protein-2 Expressing Adenoviral Vector, In: Recent Research Developments in Biophysics & Biochemistry"Research Signpost (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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