2004 Fiscal Year Final Research Report Summary
Study of osteogenetic effect on the fracture callus of facial bone by LRP5 gene transfer
| Project/Area Number |
15390625
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Tsurumi University |
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Principal Investigator |
SETO Kan-ichi Tsurumi University, School of Dental Medicine, Professor, 歯学部, 教授 (60064367)
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| Co-Investigator(Kenkyū-buntansha) |
SEKIYA Hideki Tsurumi University, School of Dental Medicine, Research Associate, 歯学部, 助手 (70267540)
KONDOU Toshiroh Ninon Univ., School of Dentistry at Matsudo, Professor, 松戸歯学部, 教授 (70178416)
TAKAGAKI Yuko Kanagawa Dental College, Associate Professor, 歯学部, 助教授 (60050689)
YAMAMOTO Matuo Kagoshima Univ., Bio-center, Associate Professor, 生命科学資源開発研究センター, 助教授 (50332896)
NEGISHI Youichi Teikyou Univ., School of Medicine, Research Associate, 薬学部, 助手 (50286978)
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| Project Period (FY) |
2003 – 2004
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| Keywords | gene transfer / distraction osteogenesis / fibrous ossification / enchondral ossification / chondrogenesis / Wnt3a / cox-2 / LRP5 |
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| Research Abstract |
The Wnt family is a group of growth factors that play an important role in almost all stages of early embryogenesis. A recent study on mice with disruption of the LRP5 gene, which encodes a co-receptor of Wnt, suggested the importance of the signal of LRP5/Wnt/β-catenin in osteochondrogenesis and bone metabolism. Accordingly, it is assumed that activation of the β-catenin signal pathway would promote osteochondrogenesis in the processes of repair. In the present study, as the transgene, we selected the Wnt3a gene in the Wnt family which activate the β-catenin signal pathway, and used a Wnt3a gene expression vector as the gene-transferring vector. We introduced the Wnt3a gene into tissue in the vicinity of bone fracture by electroporation, which is safer although less efficient than gene transfer by a viral vector, and it resulted in gene expression with relatively high efficiency when conducted under specific conditions. We investigated the effects of gene transfer of Wnt3a on the callus, which is a sheath-like structure that emerges during the healing process of bone fracture. The callus consists of fibroblasts, chondrocytes and osteoblasts that had differentiated from undifferentiated mesenchymal cells.
Introduction of the Wnt3a gene into tissue in the proximity of bone fracture by electroporation exerted locally in an autocrine/paracrine manner. Introduction of the Wnt3a gene activated the Wnt/□β-catenin signaling pathway and promoted differentiation of cartilage as observed by an increase in the volume of the callus, which plays a key role in bone fracture repair. Future studies on multi-faceted assessment of bone upon introduction of the Wnt3a gene by electroporation will be required. The present study showed that the addition of Wnt3a increased the volume of the callus, and these results may be useful for developing new treatment modalities for induction of bone regeneration in patients with its defect.
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