Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk.,Nature Communications

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Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-15 , DOI: 10.1038/s41467-019-14146-6
Lijun Wang ₁ , Xiuling You ₁ , Sutada Lotinun ₂ , Lingli Zhang ₁ , Nan Wu ₃ , Weiguo Zou _{1,

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Affiliation

Wolff's law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict the existence of a mechanostat that links strain induced by mechanical forces to skeletal remodeling. However, how the mechanostat influences bone remodeling remains elusive. Here, we find that Piezo1 deficiency in osteoblastic cells leads to loss of bone mass and spontaneous fractures with increased bone resorption. Furthermore, Piezo1-deficient mice are resistant to further bone loss and bone resorption induced by hind limb unloading, demonstrating that PIEZO1 can affect osteoblast-osteoclast crosstalk in response to mechanical forces. At the mechanistic level, in response to mechanical loads, PIEZO1 in osteoblastic cells controls the YAP-dependent expression of type II and IX collagens. In turn, these collagen isoforms regulate osteoclast differentiation. Taken together, our data identify PIEZO1 as the major skeletal mechanosensor that tunes bone homeostasis.

中文翻译：

机械感测蛋白PIEZO1通过成骨细胞-破骨细胞串扰调节骨稳态。

沃尔夫定律和犹他州的骨骼生理学范式指出，骨骼结构可以适应机械负荷。这些模型预测了将机械力引起的应变与骨骼重塑联系起来的机械稳定器的存在。然而，机械稳压器如何影响骨骼重塑仍然难以捉摸。在这里，我们发现成骨细胞中的Piezo1缺乏导致骨量减少和自发性骨折，骨吸收增加。此外，Piezo1缺陷小鼠对后肢卸载引起的进一步骨丢失和骨吸收具有抵抗力，表明PIEZO1可以响应机械力影响成骨细胞-破骨细胞串扰。在机械水平上，响应机械负荷，成骨细胞中的PIEZO1控制II型和IX型胶原的YAP依赖性表达。反过来，这些胶原同工型调节破骨细胞的分化。综上所述，我们的数据确定PIEZO1是调节骨骼动态平衡的主要骨骼机械传感器。

更新日期：2020-01-15

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