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Fluid shear stress-mediated Piezo1 alleviates osteocyte apoptosis by activating the PI3K/Akt pathway.
Zhan, Hongwei; Xie, Daijun; Yan, Zhenxing; Yi, Zhi; Xiang, Dejian; Niu, Yongkang; Liang, Xiaoyuan; Geng, Bin; Wu, Meng; Xia, Yayi; Jiang, Jin.
Afiliación
  • Zhan H; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China; Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic
  • Xie D; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: daijuncome@163.com.
  • Yan Z; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: 2446749383@qq.com.
  • Yi Z; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: yizhise@126.com.
  • Xiang D; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: dejianxiang@outlook.com.
  • Niu Y; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: niuyk21@lzu.edu.cn.
  • Liang X; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: liangxy21@lzu.edu.cn.
  • Geng B; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: cxxxf@foxmail.com.
  • Wu M; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: wumeng0330@163.com.
  • Xia Y; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: xiayylzu@126.com.
  • Jiang J; The Second Hospital of Lanzhou University, Orthopaedic Clinical Research Center of Gansu Province, Intelligent Orthopaedic Industry Technology Center of Gansu Province, Lanzhou, Gansu, China. Electronic address: jiangjin2007@163.com.
Biochem Biophys Res Commun ; 730: 150391, 2024 Oct 20.
Article en En | MEDLINE | ID: mdl-39002199
ABSTRACT
Glucocorticoid-induced osteoporosis serves as a primary cause for secondary osteoporosis and fragility fractures, representing the most prevalent adverse reaction associated with prolonged glucocorticoid use. In this study, to elucidate the impact and underlying mechanisms of fluid shear stress (FSS)-mediated Piezo1 on dexamethasone (Dex)-induced apoptosis, we respectively applied Dex treatment for 6 h, FSS at 9 dyne/cm2 for 30 min, Yoda1 treatment for 2 h, and Piezo1 siRNA transfection to intervene in MLO-Y4 osteocytes. Western blot analysis was used to assess the expression of Cleaved Caspase-3, Bax, Bcl-2, and proteins associated with the PI3K/Akt pathway. Additionally, qRT-PCR was utilized to quantify the mRNA expression levels of these molecules. Hoechst 33258 staining and flow cytometry were utilized to evaluate the apoptosis levels. The results indicate that FSS at 9 dyne/cm2 for 30 min significantly upregulates Piezo1 in osteocytes. Following Dex-induced apoptosis, the phosphorylation levels of PI3K and Akt are markedly suppressed. FSS-mediated Piezo1 exerts a protective effect against Dex-induced apoptosis by activating the PI3K/Akt pathway. Additionally, downregulating the expression of Piezo1 in osteocytes using siRNA exacerbates Dex-induced apoptosis. To further demonstrate the role of the PI3K/Akt signaling pathway, after intervention with the PI3K pathway inhibitor, the activation of the PI3K/Akt pathway by FSS-mediated Piezo1 in osteocytes was significantly inhibited, reversing the anti-apoptotic effect. This study indicates that under FSS, Piezo1 in MLO-Y4 osteocytes is significantly upregulated, providing protection against Dex-induced apoptosis through the activation of the PI3K/Akt pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteocitos / Estrés Mecánico / Dexametasona / Transducción de Señal / Apoptosis / Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt / Canales Iónicos Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteocitos / Estrés Mecánico / Dexametasona / Transducción de Señal / Apoptosis / Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt / Canales Iónicos Límite: Animals Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos