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。

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
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    2023-02-12 xjy02
  5. [GetPortalCommentsPageByObjectIdResponse(id=2026739, encodeId=9cbe2026e3914, content=<a href='/topic/show?id=e0b110159578' target=_blank style='color:#2F92EE;'>#骨关节#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101595, encryptionId=e0b110159578, topicName=骨关节)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373b263, createdName=lisa438, createdTime=Sun Jun 25 11:20:23 CST 2023, time=2023-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1858059, encodeId=05bf1858059d2, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Oct 26 22:20:23 CST 2022, time=2022-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1747060, encodeId=13881e470600f, content=<a href='/topic/show?id=495385896b5' target=_blank style='color:#2F92EE;'>#膝骨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85896, encryptionId=495385896b5, topicName=膝骨)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a9de34, createdName=zhangpaul93, createdTime=Tue Jan 17 06:20:23 CST 2023, time=2023-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084744, encodeId=9faf2084e44b6, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Sun Feb 12 05:20:23 CST 2023, time=2023-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1233371, encodeId=8a8e12333e195, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Tue Jul 19 11:37:05 CST 2022, time=2022-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1266493, encodeId=02161266493c6, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Sat Jul 16 08:20:23 CST 2022, time=2022-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1269268, encodeId=d76a1269268a0, content=<a href='/topic/show?id=59088589e97' target=_blank style='color:#2F92EE;'>#膝骨关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=85897, encryptionId=59088589e97, topicName=膝骨关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f5e185, createdName=zlawrance, createdTime=Sat Jul 16 08:20:23 CST 2022, time=2022-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435809, encodeId=1e49143580902, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11716, encryptionId=31df11e1642, topicName=microRNA)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sat Jul 16 08:20:23 CST 2022, time=2022-07-16, status=1, ipAttribution=)]
    2022-07-19 yangchou

    好文章,谢谢分享。

    0

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    2022-07-16 lmm397
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    2022-07-16 zhouqu_8

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