Hsa_circ_0001946 Ameliorates Mechanical Stress-induced Intervertebral Disk Degeneration Via Targeting miR-432-5p and SOX9.
Hsa_circ_0001946 Ameliorates Mechanical Stress-induced Intervertebral Disk Degeneration Via Targeting miR-432-5p and SOX9.
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作者：
环状RNA在椎间盘退变中的实验研究本研究旨在探讨hsa_circ_0001946（circ-CDR 1as）在机械应力诱导的IDD髓核细胞损伤中的作用。机械应力是IDD的重要致病因素。过度的压力导致髓核细胞凋亡和细胞外基质降解，加速IDD。Circ-CDR 1as与多种退行性疾病相关，但其在IDD中的作用尚不清楚。本研究旨在探讨circ-CDR 1as在IDD发病中的作用及其机制。用1.0MPa压力处理NP细胞，建立IDD体外模型。实时荧光定量聚合酶链反应检测circ-CDR 1as和miR-432- 5 p的表达。进行免疫荧光分析用于MMP 13检测。Western blot检测细胞凋亡及ECM相关蛋白表达。流式细胞术分析细胞凋亡。双荧光素酶报告基因用于分析miR-432- 5 p与circ-CDR 1as或SOX 9之间的相互作用。使用Student t检验或单因素方差分析评价组间平均值差异。在压缩处理的人NP细胞中，我们发现circ-CDR 1as显著下调。功能实验表明，circ-CDR 1as过表达减少了NP细胞中压力诱导的凋亡和ECM降解。进一步的研究表明，circ-CDR 1as可以作为miR-432- 5 p的分子海绵，miR-432- 5 p是一种通过抑制SOX 9的表达来增强NP细胞压缩诱导的损伤的miRNA。荧光素酶报告基因实验还表明，circ-CDR 1as和miR-432- 5 p之间的相互对话调节了SOX 9的表达。Circ-CDR 1as与miR-432- 5 p结合，并通过靶向SOX 9在减轻压缩诱导的NP细胞凋亡和ECM降解中起保护作用。Circ-CDR 1as可能为IDD的临床治疗提供新的靶点。
Experimental analysis of circular RNA in intervertebral disk degeneration (IDD). This study aimed to explore the roles of hsa_circ_0001946 (circ-CDR1as) in mechanical stress-induced nucleus pulposus cell injury in IDD. Mechanical stress is an important pathogenic factor for IDD. Excessive compression stress leads to nucleus pulposus (NP) cell apoptosis and extracellular matrix (ECM) degradation and accelerated IDD. Circ-CDR1as is associated with various degenerative conditions, but its role in IDD is not clear. Herein, we explored the roles and mechanisms of circ-CDR1as in IDD in vitro. An in vitro model of IDD was constructed by treating NP cells with 1.0 MPa compression stress. Quantitative real-time polymerase chain reaction assay was used for detecting the expression of circ-CDR1as and miR-432-5p. Immunofluorescent analysis was performed for MMP13 detection. Western blot assay was performed for detecting apoptosis and ECM-related protein expression. Flow cytometry analysis was used for cell apoptosis analysis. The dual-luciferase reporter was used to analyze the interaction between miR-432-5p and circ-CDR1as or SOX9. Differences in means between groups were evaluated using the Student t test or one-way analysis of variance. In compression-treated human NP cells, we found that circ-CDR1as was significantly downregulated. Functional experiments showed that circ-CDR1as overexpression reduced the compression-induced apoptosis and ECM degradation in NP cells. Further research indicated that circ-CDR1as could act as a molecular sponge for miR-432-5p, a miRNA that enhanced compression-induced damage of NP cells by inhibiting the expression of SOX9. The luciferase reporter experiments also showed that the mutual dialogue between circ-CDR1as and miR-432-5p regulated the expression of SOX9. Circ-CDR1as binds to miR-432-5p and plays a protective role in mitigating compression-induced NP cell apoptosis and ECM degradation by targeting SOX9. Circ-CDR1as may provide a novel therapeutic target for the clinical management of IDD in the future.
脂肪来源的基质细胞在受压时保护椎间盘细胞：对干细胞再生椎间盘治疗的影响
影响因子：
9.2
作者：
Sun Z;Luo B;Liu ZH;Samartzis D;Liu Z;Gao B;Huang L;Luo ZJ
通讯作者：
Luo ZJ