GNAS复合轨迹
间充质干细胞
河马信号通路
细胞生物学
基因敲除
成骨细胞
运行x2
信号转导
化学
生物
癌症研究
细胞培养
生物化学
遗传学
基因
体外
作者
Jiangdong An,Guangjie Li,Jin Zhang,Hai-Yu Zhou,Jianhua Jin,Xingwen Wang,Xiaofei Feng,Shuanke Wang
摘要
Abstract Bone marrow‐derived mesenchymal stem cells (BMSCs) are a suitable option for cell‐based tissue engineering therapies due to their ability to renew and differentiate into multiple different tissue types, such as bone. Over the last decade, the effect of GNAS on the regulation of osteoblast differentiation has attracted great attention. Herein, this study aimed to explore the role of GNAS in osteogenic differentiation of MSCs. A total of 85 GNAS f/f male mice were selected for animal experiments and 10 GNAS f/f male mice for BMSC isolation to conduct cell experiments. The mice and BMSCs were treated with Verteporfin (a Hippo signaling pathway inhibitor) to inhibit the Hippo signaling pathway or recombinant adenovirus‐expressing Cre to knockout the GNAS expression. Next, computed tomography scan, Von Kossa staining, and alizarin red staining were performed to detect osteogenic differentiation ability. Moreover, immunohistochemistry and alkaline phosphatase (ALP) staining were used to assess the expression of Oc and Osx in femur tissues and ALP activity. At last, the expression of GNAS, osteogenic markers, and factors related to the Hippo signaling pathway was evaluated. Initially, the results displayed successful knockout of the GNAS gene from mice and BMSCs. Moreover, the data indicated that GNAS knockout inhibits expression of Oc, Osx, ALP, BMP‐2, and Runx2, and ALP activity. Additionally, GNAS knockout promotes activation of the Hippo signaling pathway, so as to repress osteogenic differentiation. Collectively, depleted GNAS exerts an inhibitory role in osteogenic differentiation of MSCs by activating Hippo signaling pathway, providing a candidate mediator for osteoporosis.
科研通智能强力驱动
Strongly Powered by AbleSci AI