| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Kazuo Teikyo University, Professor, 薬学部, 教授 (30130040)
NEGISHI Youichi Tokyo University of Pharmacology, Assistant Professor, 薬学部, 講師 (50286978)
TAMURA Masato Hokkaido University, Professor, 大学院歯学研究科, 教授 (30236757)
TAKIZAWA Tomoko Teikyo University, Research Associate, 薬学部, 助手 (90260934)
SEKIYA Hideki Toho University, Assistant Professor, 医学部, 講師 (70267540)
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| Budget Amount *help |
¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Research Abstract |
A method that transfers Wnt3a genes from a non-viral vector thorough a local injection using sonoporation was proposed at sites of distracted bone.
Distraction osteogenesis was performed on a group treated with sonoporation (FGF), only with LIPUS and then the effects of the gene transfer on bone formation at a callus site of a mouse fracture model (Einhorn's method) was compared and evaluated for a comparative study,.
As a result, it was confirmed that by transferring FGF genes to the muscle tissue around callus, FGF protein was released continuously toward the callus and consequently, ossification was promoted by the FGF protein.
On the contrary, on Wnt3a transferring group, although the volume of cartilage callus increased, the ossification was not promoted.
Regarding for LIPUS group, it was revealed that ultrasound stimulation induces remodeling of bone by following reasons. By activating both an FGF signal and a COX2-PGE synthesis pathway, it promotes proliferation of osteoblasts and f
… More
ibroblasts, and the COX2-PGE synthesis pathway activated by the ultrasound activates vascular endothelial growth factor and MMPs (in submission).
It was predicted that large diameter bone will be obtained effectively by following three procedures. These are transferring Wnt3a during callus formation, transferring FGF during callus maturation and using ultrasound for helping promotion of remodeling.
In addition, performing synthesis of non-viral vectors of osteogenesis related genes such as WNT-related genes, FGF, and so forth, they were transferred to cultured bone cells by electric gene transfer (electroporation), and then encapsulation of microbubbles was attempted using the same vector with electroporation used for evaluation of expression efficiency. According to the result obtained from electroporation, gene transfer efficiency to fibrous callus is extremely low. By expressing genes through the osteogenesis related gene transfer to surrounding periosteum and muscle tissue, the effects of continuous formation and release of osteogenetic protein was obtained. Utilizing this result, an experiment system transferring microbubbles to muscle tissue and cells was established. Less
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