通过p300诱导的乳酸激素乳酸化促进骨质母细胞分化
Erika Minami1,2, Kiyohito Sasa1, Atsushi Yamada1
1Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
PloS one
|December 5, 2023
概括
在糖溶解过程中产生的乳酸酸促进了C2C12细胞中的骨质母细胞分化. 这一过程涉及到基因素乳化,一种新的表观遗传修饰,突出乳酸盐.
科学领域:
- 表观遗传学和细胞代谢
- 生物化学和分子生物学
- 干细胞分化和骨生物学
背景情况:
- 乳酸盐是通过乳酸脱酶A (LDHA) 进行无氧糖解的产物,因其在能量代谢和氧化作用中的作用而闻名.
- 基因激素乳化,最近发现的一种由乳酸中介的基因激素修饰,代表了基因调节的新机制.
- 基因素乳基化在细胞分化中的作用,特别是在骨质发生过程中,仍然在很大程度上未被探索.
研究的目的:
- 为了研究在未分化的C2C12细胞分化成骨质母细胞的过程中,组织激素乳酸化的参与和功能.
- 阐明乳酸代谢,基因素乳化和BMP-2诱导的骨质母细胞发生之间的关系.
主要方法:
- 在高 (4500毫克/升) 和低 (900毫克/升) 的葡萄糖条件下培养C2C12核细胞,以评估骨质细胞分化标志物和基因素乳化.
- 研究了LDHA抑制剂牛酸和外源乳酸补充剂对BMP-2诱导的骨质细胞分化和基因素乳化的影响.
- 通过在骨质细胞分化的背景下对基因沉默来评估p300的作用,这是一个潜在的基因激素乳化修饰剂.
主要成果:
- 高血糖条件增强了BMP-2诱导的骨质母细胞分化标志物 (Runx2,Sp7,Tnap),ALP活性和C2C12细胞中的基因素乳化.
- 用牛酸盐抑制LDHA降低了骨质母细胞分化和基因素乳化,而补充乳酸部分恢复了这些过程.
- 沉默p300损害了骨质母细胞分化和减少了基因素乳化,这表明它参与了乳化途径.
结论:
- 由LDHA合成的乳酸对BMP-2-诱导的C2C12细胞骨质细胞分化至关重要.
- 基斯乳化在促进未分化的细胞的骨质分化方面发挥着重要作用.
- 这些发现揭示了一种新的表观遗传机制,将细胞代谢与骨细胞分化联系起来.
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