Tie Kai, Tan Yang, Deng Yu, Li Jing, Ni Qubo, Magdalou Jacques, Chen Liaobin, Wang Hui
Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Reprod Toxicol. 2016 Apr;60:11-20. doi: 10.1016/j.reprotox.2015.12.010. Epub 2016 Jan 6.
Prenatal nicotine exposure (PNE) induces skeletal growth retardation and dyslipidemia in offspring displaying intrauterine growth retardation (IUGR). Cholesterol accumulation resulting from cholesterol efflux dysfunction may reduce the quality of articular cartilage through fetal programming. This study evaluated the quality of articular cartilage of female adult offspring fed a high-fat diet and explored the mechanisms using a rat IUGR model established by the administration of 2.0mg/kg/d of subcutaneous nicotine from gestational days 11-20. The results demonstrated an increased OARSI (Osteoarthritis Research Society International) score and total cholesterol content, decreased serum corticosterone, and increased IGF1 and dyslipidemia with catch-up growth in PNE adult offspring. Cartilage matrix, IGF1 and cholesterol efflux pathway expression were reduced in PNE fetuses and adult offspring. Therefore, PNE induced poor articular cartilage quality in female adult offspring fed a high-fat diet via a dual programming mechanism.
产前尼古丁暴露（PNE）会导致出现宫内生长受限（IUGR）的后代骨骼生长发育迟缓及血脂异常。胆固醇流出功能障碍导致的胆固醇蓄积可能通过胎儿编程降低关节软骨质量。本研究利用从妊娠第11至20天给予2.0mg/kg/d皮下注射尼古丁建立的大鼠IUGR模型，评估了高脂饮食喂养的成年雌性后代的关节软骨质量，并探究了其机制。结果表明，PNE成年后代的骨关节炎研究协会国际（OARSI）评分和总胆固醇含量增加，血清皮质酮降低，胰岛素样生长因子1（IGF1）增加且伴有追赶生长及血脂异常。PNE胎儿和成年后代的软骨基质、IGF1及胆固醇流出途径表达均降低。因此，PNE通过双重编程机制导致高脂饮食喂养的成年雌性后代关节软骨质量不佳。
