Mechanotransduction via the Piezo1-Akt pathway underlies Sost suppression in osteocytes
Mechanotransduction via the Piezo1-Akt pathway underlies Sost suppression in osteocytes
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DOI：
10.1016/j.bbrc.2019.10.174
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发表时间：
2020-01-15
影响因子：
3.1
通讯作者：
Nakashima, Tomoki
中科院分区：
文献类型：
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作者：
Sasaki, Fumiyuki;Hayashi, Mikihito;Nakashima, Tomoki
骨细胞通过协调成骨细胞和破骨细胞的功能，作为骨稳态的关键调节器，并且不断地暴露于机械力。然而，骨细胞中机械信号转导的分子机制还不清楚。在这里，我们发现，Yoda 1，一种选择性的Piezo 1激动剂，增加细胞内钙动员和剂量依赖性地降低表达的Sost（编码硬化蛋白）的骨细胞系IDG-SW 3。我们还证明了IDG-SW 3的机械拉伸抑制了Sost表达，这一结果通过用Piezo 1抑制剂GsMTx 4和Piezo 1的缺乏治疗而被废除。此外，通过用Akt抑制剂处理来消除对Sost表达的抑制。综上所述，这些结果表明，在骨细胞中的Piezo 1-Akt通路的激活是所需的机械拉伸诱导的下调Sost表达。(C)2019爱思唯尔公司All rights reserved.
Osteocytes function as critical regulators of bone homeostasis by coordinating the functions of osteoblasts and osteoclasts, and are constantly exposed to mechanical force. However, the molecular mechanism underlying the mechanical signal transduction in osteocytes is not well understood. Here, we found that Yoda1, a selective Piezo1 agonist, increased intracellular calcium mobilization and dose-dependently decreased the expression of Sost (encoding Sclerostin) in the osteocytic cell line IDG-SW3. We also demonstrated that mechanical stretch of IDG-SW3 suppressed Sost expression, a result which was abrogated by treatment with the Piezo1 inhibitor GsMTx4, and the deficiency of Piezo1. Furthermore, the suppression of Sost expression was abolished by treatment with an Akt inhibitor. Taken together, these results indicate that the activation of the Piezo1-Akt pathway in osteocytes is required for mechanical stretch-induced downregulation of Sost expression. (C) 2019 Elsevier Inc. All rights reserved.