| Project/Area Number |
21591960
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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 | Keio University |
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Principal Investigator |
SATO Kazuki 慶應義塾大学, 医学部, 講師 (60235322)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Kenta 慶應義塾大学, 医学部, 助教 (90383893)
川北 敦夫 独立行政法人国立成育医療研究センター, 生殖医療研究部, 共同研究員 (40338083)
梅澤 明弘 独立行政法人国立成育医療研究センター, 生殖医療研究部, 部長 (70213486)
一色 ほのか 慶應義塾大学, 医学部, 助教 (00348674)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 喫煙(ニコチン) / 喫煙 / ニコチン / 骨軟骨 / 成長障害 / 胎児・小児 |
|---|
| Research Abstract |
We investigated the effect of nicotine on human growth plate chondrocytes, a major component of enchondral ossification. The chondrocytes were derived from extra human fingers. Both human and murine growth plate chondrocytes expressed alpha7 nicotinic acetylcholine receptor(nAChR), which constitutes functional homopentameric receptors. Nicotine inhibited matrix synthesis and hypertrophic differentiation in human growth plate chondrocytes in suspension culture in a concentration-dependent manner. Methyllycaconitine(MLA), a specific antagonist of alpha7 nAChR, reversed the inhibition of matrix synthesis and functional calcium influx by nicotine in human growth plate chondrocytes in vitro. In vivo, maternal nicotine exposure resulted in delayed skeletal growth of alpha7 nAChR+/+fetuses but not in alpha7 nAChR-/-fetuses, implying that skeletal growth retardation by nicotine is specifically mediated via fetal alpha7 nAChR. These results suggest that nicotine, from cigarette smoking, acts directly on growth plate chondrocytes to decrease matrix synthesis, suppress hypertrophic differentiation, and consequently to delay enchondral ossification via alpha7 nAChR, leading to delayed skeletal growth and delayed fracture repair or non-union.
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