Mechanotransduction via the Piezo1-Akt pathway underlies Sost suppression in osteocytes |
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| Affiliation: | 1. Research Center for Ageing and Osteoporosis, Department of Diagnostics, Copenhagen University Hospital Glostrup, Glostrup, Denmark;2. Research Center for Ageing and Osteoporosis, Department of Medicine, Copenhagen University Hospital Glostrup, Glostrup, Denmark;3. The Osteoporosis and Bone Metabolic Unit, Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark;4. The Osteoporosis and Bone Metabolic Unit, Dept. of Clinical Biochemistry, Copenhagen, University Hospital Hvidovre, Hvidovre, Denmark;5. Department of Biology, University of Copenhagen, Copenhagen Ø, Denmark;6. Department of Clinical Research, Copenhagen University Hospital Glostrup, Glostrup, Denmark;7. Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark;8. Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark |
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| Abstract: | 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. |
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| Keywords: | Mechanical stimulation Mechanical signal transduction Mechanosensitive ion channel Calcium mobilization Bone homeostasis |
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