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Analysis of the interaction between BMPs and anti-sclerostin antibodies in a rat spinal immobilization model

Research Project

Project/Area Number 19K09556
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionOita University

Principal Investigator

Miyazaki Masashi  大分大学, 医学部, 講師 (30527742)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords脊椎固定 / 骨粗鬆症 / BMP / ラット / 骨折 / PTH / 抗スクレロスチン抗体
Outline of Research at the Start

ラット脊椎固定モデルにおける抗スクレロスチン抗体とBone morphogenic protein(BMP)の相互効果の検討する。ラット脊椎固定モデルを用いる。ラットの脊椎の横突起間に生食のみ、もしくはBMP(1μg)を担体とともに置く。Group I:生食のみ; Group II:BMP(1μg)にわけて実験を行う。術後、両群に抗スクレロスチン抗体を皮下投与する。手術12週間後にラットの脊椎を摘出し、徒手骨癒合試験後に、X線撮影、病理組織標本を作製する。さらにmicroCTを用いて新生骨の性状を詳細に検討する。

Outline of Final Research Achievements

A rat spine fusion model and a rat femur fracture model were established to investigate the interaction effect and safety of BMP with an anti-sclerostin antibody as an osteoporosis drug. Six weeks after the implantation of the material, the rats were sacrificed and the implanted spine and femurs were removed. After the manual bone fusion palpation test, radiographs were taken and histopathology specimens were prepared by H.E. staining. Micro-CT examination was also performed. Although no reciprocal effect between anti-sclerostin antibodies and BMP was obtained, intermittent administration of parathyroid hormone as an osteoporosis drug was found to increase bone healing ability by BMP. In this animal experimental model, the number of intermittent doses of parathyroid hormone was found to better bone fusion, depending on the number of doses administered.

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症薬であるテリパラチドとBMPの相互効果と安全性を、ラット脊椎固定モデル、ラット大腿骨骨折モデルを用いて検討した。また、テリパラチドの効果が最も発揮できる最適な投与間隔も検討した。その結果、骨粗鬆症薬であるテリパラチドと骨形成を持つBMPを併用することにより、より効果的な骨癒合が期待できる。この効果が確立できれば、脊椎固定術以外にも、骨折遷延治癒や骨欠損に対する骨再生に対しても応用可能と思われる。臨床応用された場合、骨粗鬆症を背景に持つ四肢骨折や脊椎固定術の難治性偽関節の医療費の大幅削減が可能となり日本の超高齢化社会において増大しつづける社会医療保障費の削減につながる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (4 results)

All 2021 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Optimal intermittent administration interval of parathyroid hormone 1‐34 for bone morphogenetic <scp>protein‐induced</scp> bone formation in a rat spinal fusion model2021

    • Author(s)
      Abe Tetsutaro、Miyazaki Masashi、Ishihara Toshinobu、Kanezaki Shozo、Tsubouchi Yuhta、Tsumura Hiroshi
    • Journal Title

      JOR SPINE

      Volume: 4 Issue: 3

    • DOI

      10.1002/jsp2.1168

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancement of the effects of intermittent parathyroid hormone (1-34) by bone morphogenetic protein in a rat femoral open fracture model2019

    • Author(s)
      Kanezaki Shozo、Miyazaki Masashi、Ishihara Toshinobu、Notani Naoki、Abe Tetsutaro、Tsubouchi Yuhta、Kataoka Masashi、Tsumura Hiroshi
    • Journal Title

      Journal of Orthopaedic Surgery and Research

      Volume: 14 Issue: 1 Pages: 403-403

    • DOI

      10.1186/s13018-019-1470-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] BMPを用いたラット脊椎固定モデルにおける適切なPTH1-34投与間隔の検討2021

    • Author(s)
      阿部 徹太郎、宮崎 正志, 石原 俊信,, 津村 弘
    • Organizer
      日本脊椎脊髄病学術集会
    • Related Report
      2021 Research-status Report 2020 Research-status Report
  • [Presentation] ラット大腿骨開放骨折モデルにおけるBMP-2と副甲状腺ホルモンの併用効果2019

    • Author(s)
      金崎 彰三, 宮崎 正志, 石原 俊信, 阿部 徹太郎, 野谷 尚樹, 坪内 優太, 津村 弘
    • Organizer
      日本整形外科基礎学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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