| 曹峰,程继伟,黄承,王振林.SIRT1 促进 SOX2 阻断铁死亡调控骨生成改善骨质疏松[J].浙江中西医结合杂志,2025,35(11): |
| SIRT1 促进 SOX2 阻断铁死亡调控骨生成改善骨质疏松 |
| Study on the mechanism of SIRT1 promoting SOX2 blocking iron death and regulating bone formation in osteoporosisCao Feng, Cheng Jiwei, Huang cheng, et al |
| 投稿时间：2024-11-12 修订日期：2025-07-23 |
| DOI： |
| 中文关键词: 骨质疏松，SIRT1，SOX2，铁死亡，骨髓间充质干细胞，成骨分化 |
| 英文关键词:osteoporosis, SIRT1, SOX2, ferroptosis, bone marrow mesenchymal stem cells, osteogenic differentiation |
| 基金项目:宁波市自然科学基金(2023J362), |
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| 中文摘要: |
| 目的 探究骨质疏松症(osteoporosis,OP)中 SIRT1 通过 SOX2 调节铁死亡调控骨生成的作用机制。方法 将 12 只 C57BL/6J 随机分为假手术组和模型组。分离各组原代骨髓间充质干细胞,并命名为对照组和 OP 组,之后将 OP 细胞分为 OP+oe-NC 组、OP+oe-SIRT1 组、OP+oe-SIRT1+erastin 组,OP+oe-SIRT1+si-NC 组和OP+oe-SIRT1+si-SOX2 组。使用 HE 染色和 Masson 染色分析骨小梁及骨胶原变化,使用骨密度仪检测骨密度,使用Western blot 检测 SIRT1、SOX2、铁死亡相关蛋白(SLC7A11 和 GPX4)和成骨相关蛋白(OCN、RUNX2 和 Osterix)的表达,使用碱性磷酸酶(alkaline phosphatase,ALP)和茜素红 S 染色检测细胞成骨分化和细胞钙结节,使用活性氧(reactive oxygen species,ROS)试剂盒检测细胞内 ROS。结果 与假手术组相比,模型组小鼠的骨小梁结构紊乱,胶原纤维减少,且SLC7A11、GPX4、SIRT1和SOX2的表达显著降低。与对照组相比,OP 组细胞的 ALP 活性降低,钙结节减少,ROS 增加,SIRT1、SOX2、SLC7A11、GPX4、OCN、RUNX2 和 Osterix 显著降低。与 OP+oe-NC 相比,OP+oe-SIRT1 组细胞的 ALP 活性增强,钙结节增多,ROS 下降,SIRT1、SOX2、SLC7A11、GPX4、OCN、 |
| 英文摘要: |
| Objective To explore the mechanism of SIRT1 in osteoporosis (OP) by regulating iron death through SOX2. Method Twelve female C57BL/6J mice were randomly divided into sham operation group and model group. The primary bone marrow mesenchymal stem cells of mice in each group were separated and named as control group and OP group. Then OP cells were divided into OP+oe-NC group, OP+oe-SIRT1 group, OP+oe-SIRT1+erastin group, OP+oe-SIRT1+si-NC group and OP+oe-SIRT1+si-SOX2 group. We used HE staining and Masson staining to analyze the changes of trabecular bone and bone collagen, dual energy X-ray absorptiometry to detect bone mineral density, western blot to detect the expression levels of SIRT1, SOX2, ferroptosis related proteins (SLC7A11 and GPX4), and osteogenic proteins (OCN, RUNX2 and Osterix), alkaline phosphatase (ALP) staining to detect the osteogenic differentiation of cells, alizarin red S method to detect the cell calcium nodules, and reactive oxygen species (ROS) kit to detect intracellular ROS. Result Compared with the sham operation group, the bone density, trabecular structure and collagen fibers of the model group were decreased, and the expression levels of SIRT1, SOX2, SLC7A11 and GPX4 were significantly decreased. Compared with the control group, ALP activity was decreased, calcium nodules were decreased, ROS levels were increased, and SIRT1, SOX2, SLC7A11, GPX4, OCN, RUNX2 and Osterix were significantly decreased in the OP group. Compared with OP+oe-NC group, ALP activity was enhanced, calcium nodules were increased, ROS level was decreased, and SIRT1, SOX2, SLC7A11, GPX4, OCN, RUNX2 and Osterix were significantly increased in the OP+oe-SIRT1 group. Compared with the OP+oe-SIRT1 group, ALP activity was decreased, calcium nodules were decreased, ROS levels were increased, and SLC7A11, GPX4, OCN, RUNX2 and Osterix were significantly decreased in the OP+oe-SIRT1+erastin group. Compared with OP+oe-SIRT1+si-NC group, ALP activity was decreased, calcium nodules were decreased, ROS levels were increased, and SOX2, SLC7A11, GPX4, OCN, RUNX2 and Osterix were significantly decreased in the OP+oe-SIRT1+si-SOX2 group. Conclusion SIRT1 can up-regulate SOX2 to inhibit ferroptosis and promote osteogenic differentiation of bone marrow mesenchymal stem cells to alleviate the occurrence of OP. |
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