| Project/Area Number |
14571409
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kanagawa Dental College |
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Principal Investigator |
MIKUNI-TAKAGAKI Yuko Kanagawa Dental College, Faculty of Dentistry, Associate Professor, 歯学部, 助教授 (60050689)
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| Co-Investigator(Kenkyū-buntansha) |
ITOMAN Moritoshi Kitasato Univ., Faculty of Medicine, Professor, 医学部, 教授 (70104528)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | ultrasound / bone formation / mechanotransduction / fracture repair / COX2 / prostaglandin E2 / osteoblast / disuse / 超音波骨折治療器 / アナボリック / 骨折治癒 / COX-2 / PGE_2 / ノックアウトマウス |
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| Research Abstract |
In our previous studies, we emphasized the role of COX-2 as an amplifier of mechanical response of primary and established bone cells. With that in mind, our working hypothesis was that COX-2 sustains the anabolic effect of mechanical stimuli resulting in the amplification of the initial mechanical input. We tested COX-2 null, one-year-old mice for impaired sonic accelerated fracture repair by subjecting their fractured femur to mechanical stimulation with LIPUS, low-intensity pulsed ultrasound. Choice of older mice for experimental animals was made since the fractured femur in the COX-2 knockout mice (Dinchuk, 1995) of 10 weeks of age, healed at an almost similar rate to those in normal littermates. On the other hands, we have observed the repair process, which took much longer, was not significantly accelerated by LIPUS, in the fractured femur of one-year-old knockout mice. Whether it is due t the blockade of COX-2-related mechanotransduction pathways was investigated. Downstream target molecules such as MMP-9, MMP-13 and VEGF are suggested to be essential to the inhibitory mechanism. Not only the cartilage removal in endochondral bone formation, but the development of undifferentiated osteogenic cells are affected. Both the role of COX-2 in bone formation and the possible undesirable outcome of NSAIDs use in elderly patients during the fracture repair are discussed
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