Nicotine acts on growth plate chondrocytes to delay skeletal growth through the alpha7 neuronal nicotinic acetylcholine receptor.
Nicotine acts on growth plate chondrocytes to delay skeletal growth through the alpha7 neuronal nicotinic acetylcholine receptor.
复制标题
DOI：
10.1371/journal.pone.0003945
复制
发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Umezawa A
中科院分区：
文献类型：
--
作者：
Kawakita A;Sato K;Makino H;Ikegami H;Takayama S;Toyama Y;Umezawa A
吸烟会对骨骼生长过程中的软骨内骨化产生不利影响。在众多的香烟化学物质中，尼古丁是导致吸烟引起的骨骼生长延迟的主要候选化合物之一。然而，尼古丁引起骨骼生长延迟的可能机制仍不清楚。在过去的十年中，神经元烟碱乙酰胆碱受体（nAChR）（一种尼古丁的特异性受体）的定位已在非兴奋性细胞中广泛检测到。因此，我们假设尼古丁直接并特异地通过 nAChR 影响生长板软骨细胞，从而延迟骨骼生长。我们研究了尼古丁对人生长板软骨细胞（软骨内骨化的主要成分）的影响。软骨细胞来自额外的人类手指。尼古丁以浓度依赖性方式抑制悬浮培养的人生长板软骨细胞的基质合成和肥大分化。人和鼠生长板软骨细胞均表达 α7 nAChR，它构成功能性同五聚体受体。甲基利卡乌头碱 (MLA) 是 α7 nAChR 的特异性拮抗剂，可在体外逆转人生长板软骨细胞中尼古丁对基质合成和功能性钙信号的抑制。为了研究尼古丁对体内生长板的影响，控制排卵的怀孕 α7 nAChR +/- 小鼠在怀孕期间饮用含或不含尼古丁的水，并观察其胎儿的骨骼生长。母亲接触尼古丁会导致 α7 nAChR +/+ 胎儿骨骼生长延迟，但不会影响 α7 nAChR −/− 胎儿，这意味着尼古丁引起的骨骼生长迟缓是通过胎儿 α7 nAChR 特异性介导的。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，通过 α7 nAChR 抑制肥大分化，导致骨骼生长延迟。
Cigarette smoking adversely affects endochondral ossification during the course of skeletal growth. Among a plethora of cigarette chemicals, nicotine is one of the primary candidate compounds responsible for the cause of smoking-induced delayed skeletal growth. However, the possible mechanism of delayed skeletal growth caused by nicotine remains unclarified. In the last decade, localization of neuronal nicotinic acetylcholine receptor (nAChR), a specific receptor of nicotine, has been widely detected in non-excitable cells. Therefore, we hypothesized that nicotine affect growth plate chondrocytes directly and specifically through nAChR to delay skeletal growth. We investigated the effect of nicotine on human growth plate chondrocytes, a major component of endochondral ossification. The chondrocytes were derived from extra human fingers. Nicotine inhibited matrix synthesis and hypertrophic differentiation in human growth plate chondrocytes in suspension culture in a concentration-dependent manner. Both human and murine growth plate chondrocytes expressed alpha7 nAChR, which constitutes functional homopentameric receptors. Methyllycaconitine (MLA), a specific antagonist of alpha7 nAChR, reversed the inhibition of matrix synthesis and functional calcium signal by nicotine in human growth plate chondrocytes in vitro. To study the effect of nicotine on growth plate in vivo, ovulation-controlled pregnant alpha7 nAChR +/− mice were given drinking water with or without nicotine during pregnancy, and skeletal growth of their fetuses was observed. 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 via alpha7 nAChR, leading to delayed skeletal growth.
登录
查看更多内容
影响因子：
1.6
作者：
Karatza, AA;Varvarigou, A;Beratis, NG
通讯作者：
Beratis, NG
影响因子：
12.7
作者：
OLSEN, J;PEREIRA, AD;OLSEN, SF
通讯作者：
OLSEN, SF
DOI：
10.1083/jcb.200206096
发表时间：
2002-10-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Arredondo J;Nguyen VT;Chernyavsky AI;Bercovich D;Orr-Urtreger A;Kummer W;Lips K;Vetter DE;Grando SA
通讯作者：
Grando SA
DOI：
10.1083/jcb.105.2.999
发表时间：
1987-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Tacchetti C;Quarto R;Nitsch L;Hartmann DJ;Cancedda R
通讯作者：
Cancedda R
DOI：
10.1177/140349489602400109
发表时间：
1996-03-01
期刊：
SCANDINAVIAN JOURNAL OF SOCIAL MEDICINE
影响因子：
--
作者：
Nordstrom, ML;Cnattingius, S
通讯作者：
Cnattingius, S