从乙醇代谢中获得的乙酸盐会影响骨中的基因表达,并导致基因分化延迟
Kim B Pedersen1, Cheyleann Del Valle Ponce de Leon1, Hardy Hang1
1Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, United States.
概括
酒精代谢产生酸盐,这有助于骨毒性. 乙酸可以模仿乙醇.
科学领域:
- 骨生物学 骨生物学
- 细胞和分子生物学是细胞和分子生物学.
背景情况:
- 酒精摄入量是骨质疏松症的已知危险因素,影响骨细胞和生长板.
- 肝脏中的乙醇代谢产生酸盐,增加其循环.
研究的目的:
- 调查乙酸是否调解乙醇在骨和状细胞分化中的毒性.
- 为了比较乙醇和酸盐对骨质稳态和骨生成的影响.
主要方法:
- 乙醇和乙酸通过体和腹腔内注射在体内进行.
- 评估了与骨质稳定和骨质细胞分化有关的基因表达.
- 利用ATDC5细胞在体外研究chondrogenic分化,测量基因表达和蛋白质糖生产.
- 研究了细胞外信号调节激酶 (ERK) 信号通路的作用.
主要成果:
- 乙酸的使用增加了骨质细胞分化标志物的表达 (Calcr,Ocstamp).
- 乙醇和乙酸都抑制了ATDC5细胞中的体差异化,影响了aggrecan (Acan) 和原2a1 (Col2a1) 的mRNA表达.
- 乙诱导的基生成抑制导致ERK1/ERK2酸化升高和Sox9/Runx2表达减少,通过阻断ERK.
- 通过抑制酒精脱酶,乙醇对基生成的影响并未被阻止.
结论:
- 乙醇衍生的酸介导部分诱导骨质细胞分化标志物.
- 乙酸模仿乙醇对早期原体分化的抑制作用,部分通过ERK信号通路.
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