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| 组蛋白去乙酰化酶4在大鼠骨关节炎软骨退变中的变化趋势及作用 |
| The change trend and role of HDAC4 in cartilage degeneration of rat OA model |
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| DOI：10.3969/j.issn.1006-7108.2022.11.005 |
| 中文关键词: 组蛋白去乙酰化酶4 runt相关的转录因子2 骨关节炎 大鼠 软骨细胞 |
| 英文关键词:histone deacetylase 4 Runx-2 osteoarthritis rat chondrocyte |
| 基金项目:山西省基础研究计划自然科学研究面上项目（20210302123488）；山西白求恩医院人才引进科研启动金（2021RC016）；山西省骨关节炎生物学样本资源共享服务平台建设项目（201705D121010） |
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| 中文摘要: |
| 目的 探讨组蛋白去乙酰化酶4（HDAC4）及其下游分子Runx-2在大鼠骨关节炎（osteoarthritis，OA）发生发展中的变化及对关节软骨退变的影响。方法 大鼠实验组肋软骨细胞添加10 ng/mL的IL-1β，对照组添加等体积的无菌PBS，48 h后行Western blot检测HDAC4和Runx-2的表达；构建ACLT大鼠OA模型，于术后2、4、8周通过番红固绿染色检测关节软骨退变情况，关节软骨损伤程度采用OARSI评分；同时，通过免疫组织化学染色和RT-qPCR检测HDAC4和Runx-2的表达量。结果 体外OA模型中，和对照组比，HDAC4的表达降低，Runx-2的表达升高（P＜0.05）；大鼠前交叉韧带切断组，番红固绿染色显示，大鼠术后时间的增加伴随着膝软骨破坏程度的增加，OARSI评分升高（P＜0.05）；免疫组化可见，术后的时间不断增加，HDAC4的表达逐渐降低，而Runx-2的表达逐渐升高（P＜0.05）。实时荧光定量PCR（RT-qPCR）显示，HDAC4 mRNA的表达随造模时间延长，其表达降低，而Runx-2 mRNA的表达逐渐升高（P＜0.05）。结论 在OA发生和进展过程中，HDAC4含量的不断降低，而其下游Runx-2的表达逐渐增加，可能和OA关节软骨退变相关。 |
| 英文摘要: |
| Objective To investigate the changes of HDAC4 and its downstream Runx-2 in the development of osteoarthritis (OA) in rats and their effects on articular cartilage degeneration. Methods Rat costal chondrocytes were cultured and divided into experimental group and control group. IL-1β with a final concentration of 10 ng/mL was added to the experimental group. The control group was added with sterile PBS. The expressions of HDAC4 and Runx-2 were detected with Western blotting 48 hours later. The OA model of anterior cruciate ligament transection in rats was established. The degeneration of articular cartilage was detected with Safranin O Fast green staining at 2, 4, and 8 weeks after operation. The articular cartilage injury was scored with OARSI. The expressions of HDAC4 and Runx-2 were detected using immunohistochemical staining and RT-qPCR. Results In the in vitro OA model, the HDAC4 expression decreased in experimental group, and the expression of Runx-2 increased (P<0.05). In rat ACLT OA model, Safranin O Fast green staining results showed that with extension of time after operation, the severity of cartilage degeneration increased and the OARSI score increased (P<0.05). Immunohistochemical staining results showed that with extension of time after operation, HDAC4 expression decreased gradually, and Runx-2 expression increased gradually (P<0.05). RT-qPCR results showed that the expression of HDAC4 mRNA decreased with extension of time after operation, while the Runx-2 mRNA expression increased gradually (P<0.05). Conclusion During the progression of OA, the decrease of HDAC4 and increase of Runx2 lead to the degeneration of OA cartilage. |
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