A&R：microRNA-27b-3p在膝骨关节炎滑膜纤维化反应中的作用

2022-07-19 紫菀款冬 MedSci原创

研究microRNA-27b-3p对骨关节炎滑膜纤维化的作用。

目的：滑膜纤维化导致骨关节炎（OA）病理，但其潜在机制尚不清楚。该团队观察到晚期膝关节OA患者滑液中microRNA（miR）-27b-3p水平升高。在本研究中，该团队确定了miR-27b-3p对滑膜纤维化的作用。

方法：采用原位杂交法对Kellgren-Lawrence分级膝关节OA患者和膝关节OA（内侧半月板失稳；DMM）小鼠模型的滑膜切片进行miR-27b-3p染色。研究了miR-27b-3p模拟物关节内注射对幼鼠膝关节的影响，并检测了miR-27b-3p抑制剂在DMM模型中的影响。

在人OA成纤维细胞样滑膜细胞（FL）上进行MiR-27b-3p模拟物或抑制剂转染实验，使用RT-qPCR阵列、RNA测序、RT-qPCR、Western Blot、免疫荧光和迁移分析进相关检测。

结果：MiR-27b-3p在膝OA患者滑膜和小鼠DMM手术后表达增加。在小鼠膝关节内注射miR-27b-3p模拟物可诱导滑膜纤维化样表型，滑膜炎评分增加，COL1A1和α-SMA表达增加。在DMM模型中，miR-27b-3p抑制剂在COL1A1表达和滑膜炎评分不变的情况下降低了α-SMA。

MiR-27b-3p模拟治疗人OA-FLS可诱导促纤维化反应，包括增加关键细胞外基质（ECM）基因的迁移和表达，而抑制剂转染具有相反的效果。RNA测序鉴定了OA FLS中由miR-27b-3p调节的PPARG/ADAMTS8信号轴。经PPARG激动剂罗格列酮或ADAMTS8 siRNA处理的MiR-27b-3p模拟转染的OA-FLS表现出选择性ECM基因的表达改变。

结论：该研究首次证明了miR-27b-3p及其下游信号介质在与OA期间滑膜纤维化相关的ECM调节中的关键作用。

文献来源：

Tavallaee G, Lively S, Rockel JS, et al. Contribution of microRNA-27b-3p to synovial fibrotic responses in knee osteoarthritis [published online ahead of print, 2022 Jul 6]. Arthritis Rheumatol. 2022;10.1002/art.42285. doi:10.1002/art.42285

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2023-06-25 lisa438

#骨关节#

112 0
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2022-10-26 jiafufeng@yaho

#CRO#

75 0
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2023-01-17 zhangpaul93

#膝骨#

65 0
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2023-02-12 xjy02

#Micro#

64 0
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2022-07-19 yangchou

好文章，谢谢分享。

70 0
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2022-07-16 lmm397

#关节炎#

47 0
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2022-07-16 zlawrance

#膝骨关节炎#

80 0
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2022-07-16 zhouqu_8

#microRNA#

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