利培酮通过影响Wnt/β-catenin信号通路诱导人成骨细胞系hFob1.19凋亡

doi:10.16352/j.issn.1001-6325.2023.03.374

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (3): 374-379.doi: 10.16352/j.issn.1001-6325.2023.03.374

利培酮通过影响Wnt/β-catenin信号通路诱导人成骨细胞系hFob1.19凋亡

庞兰¹, 李佩璠², 郑蕾^2*, 王艺明^2*

1.贵州医科大学,贵州贵阳 550004;
2.贵州医科大学附属医院精神科,贵州贵阳 550004

收稿日期:2022-07-07 修回日期:2022-12-03 出版日期:2023-03-05 发布日期:2023-02-27
通讯作者: * 1173765117@qq.com;754603457@qq.com
基金资助:
国家自然科学基金(81960262,82060651);贵州省重性抑郁障碍精准诊疗国际科技合作基地(黔科合人才平台[2018]5802);贵州省高层次创新型人才培养计划-百层次人才(黔科合人才平台[2016]5679); 贵州省科技计划项目(黔科合同[2020]4Y239);贵阳市科技计划项目(筑科合同[2018]1-94);贵州医科大学附属医院博士研究基金(GYFYBSKY-2021-67)

Risperidone induces apoptosis of human osteoblast cell line hFob1.19 through Wnt/β-catenin signaling pathway

PANG Lan¹, LI Peifan², ZHENG Lei^2*, WANG Yiming^2*

1. Guizhou Medical University, Guiyang 550004;
2. Department of Psychiatry, Affiliated Hospital of Guizhou Medical University,Guiyang 550004, China

Received:2022-07-07 Revised:2022-12-03 Online:2023-03-05 Published:2023-02-27
Contact: * 1173765117@qq.com;754603457@qq.com

摘要/Abstract

摘要： 目的探讨利培酮对人成骨细胞系hFob1.19凋亡的影响,并进一步分析其基于Wnt/β-catenin信号通路的分子机制。方法将hFob1.19细胞分为对照组、利培酮干预组(0、5、20、40、60、80、100和120 μmol/L)。CCK-8法检测细胞活力;流式细胞测量术检测细胞凋亡率;RT-qPCR及Western blot检测细胞BCL-2、MCL-1、BAX以及β-catenin基因及蛋白表达水平。结果 1)与对照组相比,利培酮组细胞活力呈剂量和时间依赖性下降(P＜0.05),而细胞凋亡率呈剂量依赖性增加(P＜0.05)。2)与对照组相比,利培酮组促凋亡基因BAX水平升高,而抗凋亡基因BCL-2、MCL-1水平降低,同时β-catenin的基因表达降低(P＜0.01)。3)与对照组相比,利培酮组促凋亡蛋白BAX、cleaved caspase-3水平升高,而抗凋亡蛋白BCL-2、MCL-1水平降低,同时β-catenin蛋白表达降低(P＜0.01)。4)与对照组相比,利培酮组的β-catenin蛋白在细胞核和细胞质表达均降低(P＜0.05)。结论利培酮可以诱导hFob1.19细胞凋亡,其机制可能与利培酮抑制β-catenin表达水平以及抑制β-catenin向核内转移从而导致抗凋亡蛋白质和促凋亡蛋白质平衡被打破相关。

关键词: 利培酮, 成骨细胞, 凋亡蛋白质, β-catenin

Abstract: Objective To investigate the effect of risperidone on the apoptosis of human osteoblast cell line hFob1.19 and analyze potential molecular mechanism based on Wnt/β-catenin signaling pathway. Methods hFob1.19 cells were divided into control group and risperidone intervention group (0, 5, 20, 40, 60, 80, 100 and 120 μmol/L). Cell viability was detected by CCK-8 assay. The apoptosis rate was detected by flow cytometry. RT-qPCR and Western blot was used to detect the mRNA and protein expression of BCL-2, MCL-1, BAX, and β-catenin. Results 1)Compared with the control group, the cell viability of the risperidone group decreased in a dose- and time-dependent manner (P＜0.05), while the apoptosis rate increased in a dose-dependent manner(P＜0.05). 2)Compared with the control group, the expression of pro-apoptotic gene BAX in risperidone group increased, while the expression of anti-apoptotic genes BCL-2 and MCL-1 decreased, and the expression of β-catenin decreased (P＜0.01). 3)Compared with the control group, the levels of pro-apoptotic proteins BAX and cleaved caspase-3 were increased, the levels of anti-apoptotic proteins BCL-2 and MCL-1 were decreased, and the expression of β-catenin protein was decreased in risperidone group (P＜0.01). 4) Compared with the control group, the expression of β-catenin protein in the nucleus and cytoplasm of risperidone group decreased (P＜0.05). Conclusions Risperidone induces apoptosis of hFob1.19 cells, and the mechanism may be related to the inhibition of β-catenin expression and nuclear translocation of β-catenin by risperidone, which leads to the disruption of the balance between anti-apoptotic and pro-apoptotic proteins.

Key words: risperidone, osteoblasts, apoptosis proteins, β-catenin

中图分类号:

R964

庞兰, 李佩璠, 郑蕾, 王艺明. 利培酮通过影响Wnt/β-catenin信号通路诱导人成骨细胞系hFob1.19凋亡[J]. 基础医学与临床, 2023, 43(3): 374-379.

PANG Lan, LI Peifan, ZHENG Lei, WANG Yiming. Risperidone induces apoptosis of human osteoblast cell line hFob1.19 through Wnt/β-catenin signaling pathway[J]. Basic & Clinical Medicine, 2023, 43(3): 374-379.

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利培酮通过影响Wnt/β-catenin信号通路诱导人成骨细胞系hFob1.19凋亡

Risperidone induces apoptosis of human osteoblast cell line hFob1.19 through Wnt/β-catenin signaling pathway

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