首页|miR-148a通过调节Wnt/β-catenin信号通路改善椎间盘组织退变的机制

miR-148a通过调节Wnt/β-catenin信号通路改善椎间盘组织退变的机制

Mechanism of miR-148a improving intervertebral disc tissue degeneration by regulating Wnt/β-catenin signal pathway

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目的 探讨miR-148a通过调节Wnt/β-catenin信号通路改善椎间盘退变(IDD)的机制.方法 以白细胞介素(IL)-1β诱导建立IDD大鼠和细胞模型.观察miR-148a对如下观察指标的影响:椎间盘组织病理形态,椎间盘软骨组织,椎间盘髓核细胞活力及凋亡,血清及椎间盘髓核细胞的IL-6与IL-18水平,椎间盘组织及髓核细胞机制标记物蛋白Ⅱ型胶原(Collagen Ⅱ)、蛋白聚糖(Aggrecan)的表达;椎间盘组织及髓核细胞miR-148a、Wnt/β-catenin通路相关蛋白(Wnt、β-catenin)的表达.结果 与假手术组(大鼠)/对照组(细胞)比较,模型组大鼠椎间盘组织发生退变且软骨基质大量流失,髓核细胞活力及Collagen Ⅱ、Aggrecan蛋白表达均降低(P<0.05),髓核细胞凋亡率、IL-6、IL-18、Wnt及β-catenin蛋白表达均升高(P<0.05).与模型组比较,miR-148a过表达组大鼠椎间盘组织退变及软骨基质流失症状减轻,髓核细胞活力、Collagen Ⅱ、Aggrecan蛋白表达均升高(P<0.05),髓核细胞凋亡率、IL-6、IL-18、Wnt及β-catenin蛋白表达均降低(P<0.05).结论 miR-148a可通过下调Wnt/β-catenin信号通路表达而抑制炎症,进而减轻IDD大鼠椎间盘及软骨损伤,缓解软骨基质流失及髓核细胞凋亡,改善大鼠椎间盘组织退变症状.
Objective To investigate the mechanism of miR-148a improving intervertebral disc degeneration(IDD)by regulating Wnt/β-catenin signal pathway.Methods Interleukin(IL)-1 β was inducted to establish the models of IDD rats and cells,in order to observe the influence of miR-148 on the following indicators:Pathological morphology of in-tervertebral disc tissue,intervertebral disc cartilage tissue,viability and apoptosis of intervertebral disc nucleus pulpo-sus cells,levels of IL-6 and IL-18 in serum and intervertebral disc nucleus pulposus cells,expression of protein type Ⅱ collagen(Collagen Ⅱ),proteoglycan(Aggrecan)as mechanistic markers in intervertebral disc tissue and nucleus pulposus cells;expression of miR-148a and Wnt/β-catenin pathway-related proteins(Wnt,β-catenin)in intervertebral disc tissue and nucleus pulposus cells.Results Compared with the sham operation group(rat)/control group(cell),for model group,the intervertebral disc tissue degenerated and cartilage matrix was massively lost,the viability of nu-cleus pulposus cells,the protein expression levels of Collagen Ⅱ and Aggrecan were all decreased(P<0.05),the ap-optosis rate of nucleus pulposus cells,the levels of IL-6 and IL-18,the protein expression levels of Wnt and β-catenin were all increased(P<0.05).Compared with the model group,for the miR-148a overexpression group,the interverte-bral disc tissue degeneration and the cartilage matrix loss in rats were alleviated,the viability of nucleus pulposus cells,the protein expression levels of Collagen Ⅱ and Aggrecan were all increased(P<0.05),the apoptosis rate of nucleus pulposus cells,the levels of IL-6 and IL-18,and the protein expression levels of Wnt and β-catenin were all decreased(P<0.05).Conclusions miR-148a can inhibit inflammation by down-regulating the expression of Wnt/β-catenin signal pathway,thereby reducing the damage of intervertebral disc and cartilage in IDD rats,relieving carti-lage matrix loss and nucleus pulposus cell apoptosis,and improving the degeneration symptoms of intervertebral disc tissue in rats.

miR-148aWnt/β-catenin signal pathwayintervertebral disc degenerationrats

卢斌、孟莉娟、张晨冲

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焦作市人民医院脊柱外科,河南焦作 454000

焦作市人民医院手术室,河南焦作 454000

miR-148a Wnt/β-catenin信号通路 椎间盘退变 大鼠

2024

临床骨科杂志
安徽医科大学,安徽省医学会

临床骨科杂志

CSTPCD
影响因子:1.438
ISSN:1008-0287
年,卷(期):2024.27(4)