Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan.
Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Biochem Biophys Res Commun. 2020 Jan 15;521(3):806-813. doi: 10.1016/j.bbrc.2019.10.174. Epub 2019 Nov 8.
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.
成骨细胞作为骨稳态的关键调节者，通过协调成骨细胞和破骨细胞的功能，不断受到机械力的作用。然而，成骨细胞中机械信号转导的分子机制尚不清楚。在这里，我们发现 Yoda1，一种选择性的 Piezo1 激动剂，增加了细胞内钙动员，并剂量依赖性地下调了成骨细胞系 IDG-SW3 中 Sost（编码 Sclerostin）的表达。我们还表明，IDG-SW3 的机械拉伸抑制了 Sost 的表达，这一结果被 Piezo1 抑制剂 GsMTx4 和 Piezo1 缺陷所消除。此外，用 Akt 抑制剂处理可消除 Sost 表达的抑制。总之，这些结果表明，机械拉伸诱导的 Sost 表达下调需要成骨细胞中 Piezo1-Akt 通路的激活。
