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Modulation of Bone Remodeling during Distraction Osteogenesis

Research Project

Project/Area Number 16390441
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokushima

Principal Investigator

YASUI Natsuo  THE UNIVERCITY OF TOKUSHIMA, GRADUATE SCHOOL, INSTITUTE OF HEALTH BIOSCIENCES, PROFESSOR, 大学院・ヘルスバイオサイエンス研究部, 教授 (00157984)

Co-Investigator(Kenkyū-buntansha) TAKATA Shinjiro  THE UNIVERCITY OF TOKUSHIMA, GRADUATE SCHOOL, INSTITUTE OF HEALTH BIOSCIENCES, LECTURER, 医学部・歯学部附属病院, 講師 (20284292)
MASTUI Yoshito  THE UNIVERCITY OF TOKUSHIMA, GRADUATE SCHOOL, INSTITUTE OF HEALTH BIOSCIENCES, ASSISTANT LECTURER, 大学院・ヘルスバイオサイエンス研究部, 助手 (80335348)
TAKAHASHI Mitsuhiko  THE UNIVERCITY OF TOKUSHIMA, GRADUATE SCHOOL, INSTITUTE OF HEALTH BIOSCIENCES, ASSISTANT LECTURER, 大学院・ヘルスバイオサイエンス研究部, 助手 (10372715)
NIKAWA Takeshi  THE UNIVERCITY OF TOKUSHIMA, GRADUATE SCHOOL, INSTITUTE OF HEALTH BIOSCIENCES, ASSOCIATE PROFESSOR, 大学院・ヘルスバイオサイエンス研究部, 助教授 (20263824)
TANIGUCHI Hisaaki  THE UNIVERCITY OF TOKUSHIMA, INSTITUTE FOR ENZYME RESEARCH, PROFESSOR, 分子酵素学研究センター, 教授 (10257636)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥10,000,000 (Direct Cost: ¥10,000,000)
Keywordsdistraction osteogenesis / remodeling / limb lengthening / callotasis / bisphosphonate / fibroblast growth factor / osteoactivin / chondromoduline / distranction osteogenesis / 骨形成 / リモデリング / ビスフォスフォネート / 骨形態計測
Research Abstract

The purpose of this study was to demonstrate the simultaneously activated bone resorption with activated bone formation and to investigate the role and efficacy of bisphosphonate in distraction osteogenesis. Left tibiae of 54 immature rabbits were lengthened for 3 weeks at a rate of 0.7 mm/day after a 1-week lag. Regenerated bone was quantitatively investigated by radiographic bone density, bone histomorphometry, and three-point-bending testing. Animals received either vehicle or nitrogen-containing bisphosphonate (N-BP), YM529/ONO5920 at doses of 0.4 mg/kg/w or 0.004 mg/kg/w for 6 weeks. Regenerated bone of the vehicle group showed a radiologically characteristic zone structure containing the osteopenic zones adjacent to the sclerotic zones. The regenerated bone of the 0.4-mg/kg/w group showed no osteopenic zones during the course and eventually became homogeneously radiodense. The bone volume corresponding to the osteopenic zone of this group was 5.6-fold greater compared with that of the vehicle group. The lengthened bone strength of this group was 3.3-fold greater in ultimate force than that of the vehicle group and equivalent to the contralateral tibia. The 0.004-mg/kg/w group had no substantial differences compared with the vehicle group, despite radiological enhancement of the mineralized front as well as somewhat delayed bone resorption. These results demonstrate that not only bone formation but also bone resorption is highly activated in the regenerated bone, implying high bone turnover. Sufficient N-BP caused a notable modulation in morphological properties of the regenerated bone through inhibition of highly activated bone resorption and eventually increased mechanical properties.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (33 results)

All 2006 2005 2004

All Journal Article (31 results) Book (2 results)

  • [Journal Article] Bisphosphonate Modulates Morphological and Mechanical Properties in Distraction Osteogenesis through Inhibition of Bone Resorption2006

    • Author(s)
      Takahashi M
    • Journal Title

      Bone (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Ubiquitin ligase Cb1-b down-regulates bone formation throughsuppression of IGF-1 signaling in osteoblasts duringdenervation.2006

    • Author(s)
      Suzue N
    • Journal Title

      J Bone Miner Res 21(3)(in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sp1 Family of Transcription Factors Regulates the Human a 2(XI)Collagen Gene(COL11A2)in Saos-2 Osteoblastic Cells2006

    • Author(s)
      Goto T
    • Journal Title

      J Bone Miner Res 21(5)(in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Bisphosphonate Modulates Morphological and Mechanical Properties in Distraction Osteogenesis through Inhibition of Bone Resorption.2006

    • Author(s)
      Takahashi M, et al.
    • Journal Title

      Bone (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ubiquitin ligase Cbl-b down-regulates bone formation through suppression of IGF-1 signaling in osteoblasts during denervation.2006

    • Author(s)
      Suzue N, et al.
    • Journal Title

      J Bone Miner Res 21(3)(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sp1 Family of Transcription Factors Regulates the Human α2(XI) Collagen Gene (COL11A2) in Saos-2 Osteoblastic Cells.2006

    • Author(s)
      Goto T, et al.
    • Journal Title

      J Bone Miner Res 21(5)(in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sp1 Family of Transcription Factors Regulates the Human α2(XI) Collagen Gene (COL11A2) in Saos-2 Osteoblastic Cells2006

    • Author(s)
      Goto T
    • Journal Title

      J Bone Miner Res 21(5)(in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cyclooxygenase-2 inhibitor delays fracture healing especially at an early stage in a rat fracture model2005

    • Author(s)
      Acta Orthop Scand
    • Journal Title

      Acta Orthop Scand 76(4)

      Pages: 470-474

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential Expression of VEGF Isoforms and VEGF Receptors in Cartilaginous Tumors2005

    • Author(s)
      Yukata K
    • Journal Title

      ANTICANCER RESEARCH 25

      Pages: 955-958

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Association Between Single-Nucleotide Polymorphisms in the SEC8L1 Gene, Which Encodes a Subunit of the Exocyst Complex, and Rheumatoid Arthritis in a Japanese Population2005

    • Author(s)
      Hamada D
    • Journal Title

      Arthritis & Rheumatism 52(5)

      Pages: 1371-1380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice2005

    • Author(s)
      Ogawa T
    • Journal Title

      Am J Physiol Cell Physiol 289

      Pages: 697-707

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Cyclooxygenase-2 inhibitor delays fracture healing especially at an early stage in a rat fracture model.2005

    • Author(s)
      Endo K, et al.
    • Journal Title

      Acta Orthop Scand. 76(4)

      Pages: 470-474

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential Expression of VEGF Isoforms and VEGF Receptors in Cartilaginous Tumors.2005

    • Author(s)
      Yukata K, et al.
    • Journal Title

      ANTICANCER RESEARCH 25

      Pages: 955-958

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association Between Single-Nucleotide Polymorphisms in the SEC8L1 Gene, Which Encodes a Subunit of the Exocyst Complex, and Rheumatoid Arthritis in a Japanese Population.2005

    • Author(s)
      Hamada D, et al.
    • Journal Title

      Arthritis & Rheumatism. 52(5)

      Pages: 1371-1380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice.2005

    • Author(s)
      Ogawa T, et al.
    • Journal Title

      Am J Physiol Cell Physiol. 289

      Pages: 697-707

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cyclooxygenase-2 inhibitor delays fracture healing especially at an early stage in a rat fracture model2005

    • Author(s)
      Endo K
    • Journal Title

      Acta Orthop Scand 76(4)

      Pages: 470-474

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Skeletal muscle gene expression in space-flown rats2004

    • Author(s)
      Nikawa T
    • Journal Title

      FASEBJ 18(3)

      Pages: 522-524

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Union of defects in the pars interarticularis of the lumbar spine in children and adolescents2004

    • Author(s)
      Fujii K
    • Journal Title

      J Bone Joint Surg[Br] 86-B(2)

      Pages: 225-231

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Relationship between Cathepsin B and Thrombin in Rheumatoid Arthritis2004

    • Author(s)
      Mishiro T
    • Journal Title

      J Rheumatol 31(7)

      Pages: 1265-1273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Continuous muscle stretch prevents disuse muscle atrophy and deterioration of its oxidative capacity in rat tail suspension models2004

    • Author(s)
      Sasa T
    • Journal Title

      Am J Phys Med & Rehabil 83(11)

      Pages: 851-856

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Development of Autoimmune Arthritis With Aging Via Bystander T Cell Activation in the Mouse Model of Sjogren's Syndrome2004

    • Author(s)
      Kobayashi M
    • Journal Title

      Arthritis Rheum 50(12)

      Pages: 3974-3984

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Skeletal muscle gene expression in space-flown rats.2004

    • Author(s)
      Nikawa T, et al.
    • Journal Title

      FASEBJ 18(3)

      Pages: 522-524

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Union of defects in the pars interarticularis of the lumbar spine in children and adolescents.2004

    • Author(s)
      Fujii K, et al.
    • Journal Title

      J Bone Joint Surg [Br] 86-B(2)

      Pages: 225-231

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Relationship between Cathepsin B and Thrombin in Rheumatoid Arthritis.2004

    • Author(s)
      Mishiro T, et al.
    • Journal Title

      J Rheumatol 31(7)

      Pages: 1265-1273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Continuous muscle stretch prevents disuse muscle atrophy and deterioration of its oxidative capacity in rat tail suspension models.2004

    • Author(s)
      Sasa T, et al.
    • Journal Title

      Am J Phys Med & Rehabil 83(11)

      Pages: 851-856

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of Autoimmune Arthritis With Aging Via Bystander T Cell Activation in the Mouse Model of Sjogren's Syndrome.2004

    • Author(s)
      Kobayashi M, et al.
    • Journal Title

      Arthritis Rheum. 50(12)

      Pages: 3974-3984

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Skeletal muscle gene expression in space-flown rats2004

    • Author(s)
      Nikawa T
    • Journal Title

      FASEBJ 18

      Pages: 522-524

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Influence of age on scapulo-thoracic orientation2004

    • Author(s)
      Endo K
    • Journal Title

      Clinical Biomechanics 19

      Pages: 1009-1013

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Vertebral forward slippage in immature lumbar spine occurs following epiphyseal separation and its occurence is unrelated to disc degeneration. Is the pediatric spondylolisthesis a physis stress fracture of vertebral body?2004

    • Author(s)
      Sairyo K
    • Journal Title

      Spine 29(5)

      Pages: 524-527

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Muscular oxidative capacity in ovariectomized rats : Discussion on the endurance performance of female athletes with sports-related amenorrhea2004

    • Author(s)
      Sasa T
    • Journal Title

      J Sports Sci & Med

      Pages: 15-22

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anti-alpha-fodrin autoantibodies in Moyamoya disease2004

    • Author(s)
      Ogawa K
    • Journal Title

      Stroke 34(12)

    • Related Report
      2004 Annual Research Report
  • [Book] 標準整形外科学 : 骨系統疾患2005

    • Author(s)
      安井夏生
    • Total Pages
      20
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] キャンベル整形外科手術書3(非外傷性軟部組織疾患・先天異常)2004

    • Author(s)
      安井夏生
    • Total Pages
      340
    • Publisher
      エルセビア・ジャパン
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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