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The Studies Regarding Gene Transfer for the Promotion of Bone Ligament Healing

Research Project

Project/Area Number 14571360
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HIRAOKA Hisatada  The Univ. of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (10262007)

Co-Investigator(Kenkyū-buntansha) TANAKA Sakae  The Univ. of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (50282661)
YAMAMOTO Motoi  The Univ. of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (00272584)
MORI Yoshihisa  The Univ. of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (60343141)
NAKAMURA Kozo  The Univ. of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (60126133)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsadenovirus vector / Ligament-to-bone healing / Gene therapy / アデノウィルススベクター / 靭帯 / アデノウイルス
Research Abstract

First, as a preliminary experiment, we applied adenovirus vectors encoding either ALK 3,5,6 or Smad 1 cDNA to the bone marrow cavity of mice and rabbits to examine the effect of these molecules on bone formation. The efficiency of gene transduction was evaluated with immunostaining. To evaluate the new bane formation we used soft X-ray, DEXA and histological examination. As we expected, enough expression level of the genes introduced locally was achieved. The LacZ gene expression was maintained for at least2 weeks. ALK 3 and 6 could promote bone formation in the bone marrow cavity at 3 weeks after surgery. Next we made an animal model, of ligament-bone-healing with rabbits and examined the effect of locally administered adenovirus vectors encoding ALK 3,5,6 or Smad 1 on ligament-bone-healing. Unfortunately, however, there was no obvious difference between the ALK administered groups and control group at any time-point from 1 week to 6 weeks after surgery. We speculated the reasons why there was no difference between these groups as follows, 1) insufficient gene transduction to achieve significantly firm anchoring of tendon to bone 2) deteriorating effect of adenovirus to the tendon substance 3) mechanical property of newly formed bone. Following this research we are going to study the effect of combination of these molecules with adenoviral gene transduction.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (1 results)

All Other

All Publications (1 results)

  • [Publications] Nakamura I, Kadono Y, Takayanagi H, Jimi E, Miyazaki T, Oda H, Nakamura K, Tanaka S, Rodan GA, Duong LT: "IL-1 Regulates Cytoskeletal Organization in Osteoclasts Via TNF Receptor-Associated Factor 6/c-Src Complex"J Immunology. 168. 5103-5109 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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