Experimental Study on Nicotine-Nicotine acts directly on growth plate chondrocytes to delay enchondral ossification through the alpha7 homopentameric neuronal nicotinic acetylcholine receptor-

尼古丁的实验研究-尼古丁通过α7同五聚体神经元烟碱乙酰胆碱受体直接作用于生长板软骨细胞延缓软骨骨化-

• 批准号: 21591960
• 负责人: SATO Kazuki
• 金额: $ 2.91万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591960/
• 关键词: 喫煙(ニコチン); 喫煙; ニコチン; 骨軟骨; 成長障害; 胎児・小児

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.

我们研究了尼古丁对人生长板软骨细胞的影响，软骨细胞是软骨成骨的主要组成部分。软骨细胞来源于多余的人类手指。人和小鼠生长板软骨细胞均表达α - 7烟碱乙酰胆碱受体（nAChR），该受体构成功能性同戊二聚体受体。尼古丁对悬浮培养的人生长板软骨细胞的基质合成和增生性分化具有浓度依赖性。甲基莱卡乌碱（MLA）是α 7 nAChR的特异性拮抗剂，可逆转尼古丁对体外人生长板软骨细胞基质合成和功能性钙内流的抑制作用。在体内，母体尼古丁暴露导致α 7 nAChR+/+胎儿骨骼生长迟缓，而α 7 nAChR-/-胎儿骨骼生长迟缓，这表明尼古丁通过胎儿α 7 nAChR特异性介导骨骼生长迟缓。这些结果表明，吸烟产生的尼古丁直接作用于生长板软骨细胞，减少基质合成，抑制肥厚分化，从而通过α - 7 nAChR延缓软骨内成骨，导致骨骼生长延迟，骨折修复或不愈合延迟。

项目成果

Nicotine acts on growth plate chondrocytes to delay skeletal growth through the alpha7 neuronal nicotinic acetylcholine receptor.

• DOI: 10.1371/journal.pone.0003945
• 发表时间: 2008
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kawakita A;Sato K;Makino H;Ikegami H;Takayama S;Toyama Y;Umezawa A
• 通讯作者: Umezawa A