与G蛋白结合的受体ADGRG6通过IHH信号来维持小鼠生长板的稳态
Fangzhou Bian1, Victoria Hansen2, Hong Colleen Feng1
1Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90033, United States.
概括
粘附G蛋白结合受体ADGRG6/GPR126通过维持生长板的恒常性,对骨生长至关重要. 缺少它会破坏胆细胞的功能,影响小鼠的增殖,分化和整体骨发育.
科学领域:
- 骨生物学 骨生物学
- 细胞生物学 细胞生物学
- 分子遗传学 分子遗传学
背景情况:
- 软骨生长板对于骨延长至关重要,但调节其出生后平衡的机制仍然不清楚.
- 了解这些机制是解决骨生长障碍的关键.
研究的目的:
- 为了研究ADGRG6/GPR126的作用,一个软骨丰富的粘附性G蛋白结合受体 (GPCR),在产后生长板的稳态中.
- 阐明ADGRG6/GPR126如何影响状细胞行为和骨生长.
主要方法:
- 利用小鼠分子遗传学 (Col2a1Cre和AcanCreERT2模型) 在特定细胞群中消去Adgrg6.
- 在甲固定,嵌组织上使用空间转录学来分析基因表达模式.
- 研究了ADGRG6/GPR126,副甲状腺激素相关蛋白 (PTHrP) 和印度刺 (IHH) 信号通路之间的相互作用.
主要成果:
- 构成性Adgrg6切除导致休息区缩短,冠状细胞增殖/分化发生变化,以及带有失调的PTHrP和IHH信号的延长型多变区.
- 在成熟的冠状细胞中产后的Adgrg6移除减少了生长板的厚度,增加了静止区细胞死亡,并损害了冠状细胞的增殖/分化.
- 空间转录学揭示了ADGRG6调节骨质生和代谢基因以及潜在的SOX9表达,在成长板区域中维持胆细胞平衡.
结论:
- ADGRG6/GPR126对于维持产后生长板平衡,调节状细胞增殖,分化和生存至关重要.
- ADGRG6/GPR126通过调节PTHrP/IHH信号和SOX9表达来影响骨生长.
- 这项研究强调了粘附性GPCRs在骨发育和生长板功能中的关键作用.
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