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Establishment of periodontal regenerative therapy using BMPs

Research Project

Project/Area Number 08557105
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Conservative dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

ISHIKAWA Isao  Tokyo Med. & Dent.Univ., Fac.of Dent., Professor, 歯学部, 教授 (10014151)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Eiichi  Tokyo Med. & Dent.Univ., Fac.of Dent., Instructor, 歯学部, 助手 (20242208)
KINOSHITA Atsuhiro  Tokyo Med. & Dent.Univ., Fac.of Dent., Instructor, 歯学部, 助手 (10242207)
ODA Shigeru  Tokyo Med. & Dent.Univ., Fac.of Dent., Lectuere, 歯学部, 講師 (70160869)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1996: ¥7,400,000 (Direct Cost: ¥7,400,000)
KeywordsBMP / Bone Morphogenetic Protein / Regenerative Therapy / Periodontal Regeneration / Furcation Involvement / Polylactic acid-polyglycolic acid coplymer / 根分岐部病変 / ポリ乳酸ポリグリコール酸共重合体 / 実験的歯周炎 / リン酸カルシウム
Research Abstract

RhBMP-2 was implanted to subcutaneous tissue of rats with three different types of carriers, including biphasic calcium phosphate (BCP), to evaluate ectopic bone formation histologically. All four samples of BCP-BMP group demonstrated bone-like tissue formation, and two of four demonstrated new bone formation with lamellae-like structure. No bone-like tissue formation was found in control groups.
RhBMP-2/PLGA gelatin sponge was implanted in bone defects in rat mandible. The animals were sacrificed at four weeks and the bone formation was evaluated histologically. The defects were completely filled with newly formed bone in four samples out of eight experimental ones, while new bone formation was very limited in the control group. The amount of the new bone formation was significantly larger in the rhBMP-2-implanted sites as compared to the control sites.
Through-and-through furcation defects were created at bilateral lower 2nd, 3rd, and 4th premolars in six beagle dogs. RhBMP-2/PGS was i … More mplanted in the experimental sites, whereas PGS alone was implanted in control sites. Histological evaluation was performed at ten weeks. Most of the furcation defects in the experimental sites were completely filled with newly formed bone. Significantly larger amounts of new bone and connective tissue attachment were shown in the experimental group as compared to the control group. No significant difference could be found in the amount of new cementum formation between the groups. Sites with large amount of new bone formation demonstrated ankylosis in both the experimental and the control groups.
Through-and-through furcation defects were made at bilateral lower 1st and 2nd molars of six rhesus monkeys, and histological evaluation was performed at 12 weeks with the same design as the experiment using beagle dogs. Amounts of new bonformation were significantly larger in the experimental group. Two out of twelve defects in the experimental sites were completely filled with new bone, and one of twelve in control sites was. No ankylosis was observed.
These results indicate that rhBMP-2 has an effect of ectopic bone formation, and promote periodontal tissue regeneration. Less

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (57 results)

All Other

All Publications (57 results)

  • [Publications] Higuchi T et al.: "BoneRegeneration by Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Rat Mandibular Defects. An Experimental Model of Defect Filling." Journal of Periodontology. 70. in press (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morotome Y et al.: "Gene Expressionof Growth and Differentiation Factors-5,-6,and -7 in Developing Bovine Tooth at the Root Forming Stage" Biochemical and BiophysicalResearch Communication. 244・1. 85-90 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 石川 烈 他: "歯周組織の細胞分化と再生への応" 日本歯科医学会雑誌. 16・1. 19-23 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morotome Y et al.: "Molecular cloning of PCRamplified BMP-related Genes (GDF-5,6,and 7) from rat tooth cellsusing modified pBluescript SK+ vector" Journal of Hard TissueBiology. 16・1. 16-20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 吉野敏明 他: "骨組織へのEr:YAGレーザー照射の影響について -ラット頭頂骨への照射後のSEMおよび組織学的観察-" 日本歯科保存学雑誌. 40・4. 1154-1164 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oda S et al.: "I: EctopicBone Formation by Biphasic Calcium Phosphate (BCP) Combinedwith Recombinant Human Bone Morphogenetic Protein-2(rhBMP-2)" Journal of Medical and Dental Science. 44・3. 53-62 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小牧基浩 他: "BMPの作用と生理的意義-臨床応用に向けて -最近の歯学-" 口腔病学会雑誌. 63・2. 430 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aoki A et al.: "Evauation of inadvertent irradiatiorr of the Er:YAG Laseron soft tssue" International Laser Congress. 267-271 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aoki A et al.: "The Effects of Mis-irradiation of the Er:YAG Laser on Softand Bone Tissues" 5th Congress of the International Society for Laserin Dentistry. 27-32 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kinoshita A et al.: "Periodontal Regeneration by Application of Recombinant HumanBone Morphogenetic Protein-2 to Horizontal Circumferential Defects Created by Experimental Periodontitis in Beagle Dogs" Journal of Periodontology. 68・2. 103-109 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 大野純一 他: "ラット舌に対するEr:YAGレーザー照射の影響について -臨床における誤照射を想定した各種条件下での照射後の肉眼およびSEM観察-" 日本レーザー歯学誌. 7・1. 46-57 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishikawa I et al.: "Cervical CementalTears in Older Patients with Adult Periodontitis.Case Reports" Journal of Periodontology. 67・1. 15-20 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小田 茂 他: ":二相性リン酸カルシウム(Biphasic Calcium Phosphate)を担体としたリコンビナントBMP-2(rhBMP-2)の異所性骨形成能について." 口腔病学会雑誌. 63・3. 468-477 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 石川 烈 他: "Recombinant humanbone morphogenetic protein-2の歯周組織に対する影響" 炎症. 16・3. 181-185 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Komaki M et al.: "Bone morphogenetic protein-2 doesnot alter the differentiation pathway of committed progenitors ofosteoblasts and chondroblasts" Cell and Tissue Research. 284・1. 9-17 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 小田 茂 他: "別冊ザ・クインテッセンス 臨床家のための矯正YEAR BOOK 98 骨誘導システムBMPの開発 rhBMPの歯周組織再生療法への応用" クインテッセンス出版, 291 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 諸留よう子 他: "別冊ザ・クインテッセンス TEAR BOOK 1998 歯科年鑑 各種GROWTH FACTORの歯周治療への応用" クイテッセンス出版, 377 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 石川 烈 他: "歯周病学" 永末書店, 296 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi T et al: "Bone Regeneration by Recombinant Human Bone Morphogenetic Protein-2(rhBMP-2)in Rat Mandibular Defects." Journal of Periodontology. Vol.70. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morotome Y et al.: "Gene Expression of Growth and Differentiation Factors-5, -6, and-7 in Developing Bovine Tooth at the Root Forming Stage." Biochemical and Biophysical Research Communications. Vol.244.85-90 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishikawa I et al.: "Cell Differentiation Mechanisms of the Periodontal Tissue and Its Application to Regenerative Therapy" Journal of Japanese Association for Dental Science. Vol.16.19-23 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morotome Y et al.: "Molecular cloning of PCR amplified BMP-relatedGenes (GDF-5,6, and7) from rat tooth cells using modified pBluescript SK+vector" Journal of Hard Tissue Biology. Vol.6.16-20 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino et al.: "The Effect of Er : YAG Laser Irradiation on the Bone Tissue-SEM and Histological after Irradiation on the Parietal Bone of Rat-" Japan Journal of Conservative Dentistry. Vol.40. 1154-1164 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oda S et al.: "Ectopic Bone Formation by Biphasic Calcium Phosphate (BCP) Combined with Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)." Journal of Medical and Dental Sciences. Vol.44.53-62 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aoki A etal.: "Evauation of Inadvertent Irradiation of the Er : YAG Laser on Soft Tissue" International Laser Congress. 267-271 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kinoshita A et al.: "Periodontal Regeneration by Application of rhBMP-2 to Horizontal Circumferential Defects Created by Experimental Periodontitis in Beagle Dogs." Journal of Periodontology. Vol.68.103-109 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Aoki A et al.: "The Effects of Mis-irradiation of the Er : YAG Laser on Soft and Bone Tissues" 5th Congress of the International Society for Laser in Dentistry. 1996. 27-32

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohno J et al.: "The Effect of the Er : YAG Laser on the Tongue of Rat-Macroscopic and SEM observations after Irradiation under Various Conditions Supposing the side Effect of Mis-irradiation-" Journal of Japanese Society for Laser Dentistry. Vol.7.46-57 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishikawa I et al.: "Cervical Cemental Tears in Older Patients with Adult Periodontitis.Case Reports" Journal of Periodontology. Vol.67.15-20 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Oda S et al.: "Ectopic Bone Induction in Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Combined with Biphasic Calcium Phosphate (BCP)" The Journal of The Stomatological Society. Vol.63.468-477 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishikawa I et al.: "The Effects of Recombinant Human Bone Morphogetic Protein-2 (rhBMP-2) on Periodontal Tissues" Japanese Journal of Inflammation. Vol.16.181-185 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Komaki M et al: "Bone morphogenetic protein-2 does not alter the differentiation pathway of committed progenitors of osteoblasts and chondroblasts" Cell and Tissue Research. Vol.284. 9-17 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishikawa I et al.: Periodontology. Nagasue Shoten Co., Ltd., Kyoto, 291 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi T et al.: "Bone Regeneration by Recombinant Human Bone Morphogenetic Protein-2(rhBMP-2)in Rat Mandibular Defects." Journal of Periodontology. 70. in press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oda S et al.: "Ectopic Bone Formation by Biphasic Calcium Phosphate(BCP)Combined with Recombinant Human Bone Morphogenetic Protein-2(rhBMP-2)." Journal of Medical and Dental Sciences. 44・3. 53-62 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kinoshita A et al.: "Periodontal Regeneration by Application of rhBMP-2 to Horizontal Circumferential Defects Created by Experimental Periodontitis in Beagle Dogs." J Periodontol. 68・2. 103-109 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ishikawa I et al.: "Cervical Cemental Tears in Older Patients with Adult Periodontitis.Case Reports." J Periodontol. 67・1. 15-20 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] 石川 烈 他: "Recombinant Human Bone Morphogenetic Protein-2の歯周組織に対する影響" 炎症. 16・3. 181-185 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小田 茂 他: "二相性リン酸カルシウム(Biphasic Calcium Phosphate)を担体としたリコンビナント BMP-2(rhBMP-2)の異所性骨形成能について" 口腔病学会雑誌. 63. 468-477 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] 小田 茂 他: "別冊ザ・クインテッセンス 臨床家のための矯正YEAR BOOK 98 骨誘導システムの開発 rhBMP-2の歯周組織再生療法への応用" クインテッセンス出版, 291 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 石川 烈 他: "歯周病学" 永末書店, 296 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oda S et al.: "Ectopic Bone Formation by Biphasic Calcium Phosphate (BCP) Combined with Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)." Journal of Medical and Dental Sciences. 44・3. 53-62 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kinoshita A et al.: "Periodontal Regeneration by Application of rhBMP-2 to Horizontal Circumferential Defects Created by Experimental Periodontitis in Beagle Dogs." J Periodontol. 68・2. 103-109 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishikawa I et al.: "Cervical Cemental Tears in Older Patients with Adult Periodontitis. Case Reports." J Periodontol. 67・1. 15-20 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 石川烈他: "Recombinant Human Bone Morphogenetic Protein-2の歯周組織に対する影響" 炎症. 16・3. 181-185 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小田茂他: "二相性リン酸カルシウム(Biphasic Calcium Phosphate)を担体としたリコンビナントBMP-2(rhBMP-2)の異所性骨形成能について" 口腔病学会雑誌. 63. 468-477 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Uoshima MH et al.: "Clinical and Histological Observation on Replacement of Biphasic Calcium Phosphate by Bone Tissue in Monkeys." The International Journal of Periodontics & Restrative Dentistry. 15・2. 205-213 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 石川烈他: "歯周病学" 永末書店, 296 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 石川烈他: "先進歯科技術と新臨床(増原栄一編)歯周病の診断と初期治療,再生治療のプログラム" Recombinant Human Bone Morphogenetic Protein-2の歯周組織に対する影響, 252 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishikawa I: "Regenerative Therapy in Periodontal Diseases,-Histological Observations after Implantation of rhBMP-2 in the Surgically Created Periodontal Defects in Adult Dogs.-" Dentistry in Japan. 31・1. 141-146 (1994)

    • Related Report
      1996 Annual Research Report
  • [Publications] Uoshima MH: "Clinical and Histological Observation on Replacement of Biphasic Calcium Phosphate by Bone Tissue in Monkeys" The International Journal of Periodontics & Restorative Dentistry. 15・2. 205-213 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ishikawa I: "Cervical Cemental Tears in Older Patients with Adult Periodontitis.Case Reports" J Periodontol. 67・1. 15-20 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 石川烈: "Recombinant human bone morphogenetic protein-2の歯周組織に対する影響" 炎症. 16・3. 181-185 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Watanabe H: "Clinical Assessments of the Erbium : YAG Laser for Soft Tissues Surgery and Scaling" J Clin Laser Med Surg. 14・2. 67-75 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kinoshita A: "Periodontal Regeneration by Application of rhBMP-2 to Horizontal Circumferential Defects Created by Experimental Periodontitis in Beagle Dogs" J Periodontol. 68・2(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 石川烈: "歯周病学" 永末書店, 296 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 石川烈: "先進歯科技術と新臨床(増原英一編) 歯周病の診断と初期治療,再生治療のプログラム" 医歯薬出版, 252 (1995)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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