通过 P2Y2 受体的嘌呤能信号调节骨细胞的机械敏感性

IF 7.4 1区 生物学 Q1 CELL BIOLOGY
Journal of Cell Biology Pub Date : 2024-11-04 Epub Date: 2024-08-30 DOI:10.1083/jcb.202403005
Amit Chougule, Chunbin Zhang, Nickolas Vinokurov, Devin Mendez, Elizabeth Vojtisek, Chenjun Shi, Jitao Zhang, Joseph Gardinier
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引用次数: 0

摘要

成骨细胞对动态负荷的反应在调节骨量方面起着至关重要的作用,但很快就会饱和,从而使下游骨形成诱导作用趋于平稳。下调骨细胞对负荷的敏感性和整体反应的潜在机制仍不清楚。在其他细胞类型中,通过 P2Y2 受体发出的嘌呤能信号有可能通过肌动蛋白聚合和细胞骨架组织改变细胞硬度,从而下调对负荷的敏感性。在此,我们使用 P2Y2 基因敲除细胞系和条件性基因敲除小鼠研究了 P2Y2 激活在调节骨细胞机械传导中的作用。我们的研究结果表明,MLO-Y4 细胞中 P2Y2 表达的缺失会阻止肌动蛋白聚合,同时增加对流体流动诱导的剪切应力的敏感性。在条件性基因敲除小鼠中删除骨细胞的 P2Y2 表达,可使骨形成在延长运动时间时增加。总之,P2Y2 在负荷下激活会产生负反馈回路,通过肌动蛋白应力纤维的形成改变骨细胞对机械应变的敏感性,从而限制骨细胞对持续负荷的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Purinergic signaling through the P2Y2 receptor regulates osteocytes' mechanosensitivity.

Osteocytes' response to dynamic loading plays a crucial role in regulating the bone mass but quickly becomes saturated such that downstream induction of bone formation plateaus. The underlying mechanisms that downregulate osteocytes' sensitivity and overall response to loading remain unknown. In other cell types, purinergic signaling through the P2Y2 receptor has the potential to downregulate the sensitivity to loading by modifying cell stiffness through actin polymerization and cytoskeleton organization. Herein, we examined the role of P2Y2 activation in regulating osteocytes' mechanotransduction using a P2Y2 knockout cell line alongside conditional knockout mice. Our findings demonstrate that the absence of P2Y2 expression in MLO-Y4 cells prevents actin polymerization while increasing the sensitivity to fluid flow-induced shear stress. Deleting osteocytes' P2Y2 expression in conditional-knockout mice enabled bone formation to increase when increasing the duration of exercise. Overall, P2Y2 activation under loading produces a negative feedback loop, limiting osteocytes' response to continuous loading by shifting the sensitivity to mechanical strain through actin stress fiber formation.

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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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