在介酶干细胞中,BMP9通过mTORC1/Stat3途径通过上调LGR4诱导骨质分化
Jie Zhang1,2, Jinhai Jiang1,2, Hang Liu2,3
1Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
Genes & diseases
|January 31, 2024
概括
含G蛋白结合受体4 (LGR4) 的氨酸丰富的重复增强骨形态蛋白9 (BMP9) 诱导的骨愈合. BMP9通过mTORC1/Stat3信号调节LGR4,促进骨质生成.
科学领域:
- 整形外科和再生医学
- 分子生物学和细胞信号传递
背景情况:
- 骨缺陷和非结合性骨缺陷带来了重大的临床挑战,治疗结果低于最佳.
- 骨组织工程,利用诸如骨形态遗传蛋白9 (BMP9) 等因素,提供了一个有前途的治疗途径.
- 含有G蛋白结合受体4 (LGR4) 的氨酸丰富的重复在骨发育中起着至关重要的作用.
研究的目的:
- 为了研究LGR4在BMP9诱导的骨质生成中LGR4的作用.
- 阐明连接LGR4和BMP9信号的基础分子机制.
主要方法:
- 在BMP9-Knockout小鼠骨髓 stromal 细胞中对LGR4表达的分析.
- 用BMP9治疗C3H10T1/2细胞并操纵LGR4水平 (过度表达和抑制).
- 评估骨质生和脂质生标志物,并调查涉及Raptor和Stat3.3的mtORC1/Stat3通路.
主要成果:
- BMP9-淘汰赛细胞显示LGR4表达减少;外源LGR4恢复了骨质生成潜力.
- BMP9增加了C3H10T1/2细胞中的LGR4表达,这反过来又增强了骨质生成.
- 抑制LGR4降低了BMP9诱导的骨质生成和增加了脂质生成;猛禽/Stat3通路参与其中.
结论:
- LGR4显著增强BMP9驱动的骨质母细胞分化和骨形成.
- BMP9上调LGR4表达,可能通过mTORC1/Stat3信号通路的激活.
- 准LGR4-BMP9轴为骨缺陷修复提供了一个潜在的战略.
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