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Matrix Biol：研究揭示OA软骨中发生改变的miRNA的功能

2018-09-09 MedSci MedSci原创

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Hedgehog（Hh）信号传导通路在胚胎发育和成体组织稳态（例如软骨）中起重要作用，其失调可导致骨关节炎（OA）。microRNA（miRNA）是基因表达的重要调节因子，参与信号传导通路（包括Hh）的调节，从而影响发育和疾病。本研究旨在确定其表达在OA软骨中发生改变的miRNA的功能。 在这里，我们确定了OA软骨中miR-324-5p的表达增加，并假设胶质瘤中miR-324-5p将调节Hh

Hedgehog（Hh）信号传导通路在胚胎发育和成体组织稳态（例如软骨）中起重要作用，其失调可导致骨关节炎（OA）。microRNA（miRNA）是基因表达的重要调节因子，参与信号传导通路（包括Hh）的调节，从而影响发育和疾病。本研究旨在确定其表达在OA软骨中发生改变的miRNA的功能。

在这里，我们确定了OA软骨中miR-324-5p的表达增加，并假设胶质瘤中miR-324-5p将调节Hh信号传导。我们确定miR-324-5p调节人间充质干细胞（MSCs）和小鼠C3H10T1/2细胞中的骨生成。荧光素酶报告基因测定表明，miR-324-5p直接调节人类而非小鼠中的靶标GLI1和SMO，表明Hh通路调节的物种依赖性机制。

进一步实时RT-PCR、免疫印迹证实和3'UTR-荧光素酶报告基因确定了小鼠中的磷脂酰肌醇蛋白聚糖1（Gpc1）是miR-324-5p新的靶标。敲除Gpc1降低了Hh通路活性，并且模拟了miR-324-5p对骨生成的影响，表明miR-324-5p通过直接靶向Gpc1调节小鼠中的Hh信号传导。最后，我们发现人GPC1不是miR-324-5p的直接靶标。

重要的是，除了鉴定Hedgehog（Ihh）信号传导的新调控外，本研究还展示了miRNA如何在两个物种中显示保守的通路调控，但是通过不同的机制，突出了人类疾病和小鼠模型之间的重要差异。

原始出处：

Woods S, Barter MJ, et al., miR-324-5p is up regulated in end-stage osteoarthritis and regulates Indian Hedgehog signalling by differing mechanisms in human and mouse. Matrix Biol. 2018 Sep 4. pii: S0945-053X(18)30200-2. doi: 10.1016/j.matbio.2018.08.009.

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    2019-06-06 smallant2002

    #miR#

    0

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    2019-02-16 freve

    #MATRix#

    0

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    2019-04-24 12498ebem31暂无昵称

    #Biol#

    0

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    2019-08-03 sunylz

    #Bio#

    0

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    2018-09-11 Homburg

    #miRNA#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1930646, encodeId=e170193064672, content=<a href='/topic/show?id=22f61180211' target=_blank style='color:#2F92EE;'>#miR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11802, encryptionId=22f61180211, topicName=miR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a27288, createdName=smallant2002, createdTime=Thu Jun 06 00:50:00 CST 2019, time=2019-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034043, encodeId=697d2034043bf, content=<a href='/topic/show?id=9613113283e' target=_blank style='color:#2F92EE;'>#MATRix#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11328, encryptionId=9613113283e, topicName=MATRix)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ced3193, createdName=freve, createdTime=Sat Feb 16 09:50:00 CST 2019, time=2019-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767512, encodeId=66341e6751251, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Wed Apr 24 23:50:00 CST 2019, time=2019-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918280, encodeId=95441918280f5, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Sat Aug 03 10:50:00 CST 2019, time=2019-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312353, encodeId=8b4d1312353bb, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11933, encryptionId=e5571193321, topicName=miRNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87d405, createdName=Homburg, createdTime=Tue Sep 11 09:50:00 CST 2018, time=2018-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344196, encodeId=8fd93441964c, content=不错的文章值得拥有哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Sun Sep 09 21:26:19 CST 2018, time=2018-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344185, encodeId=78d4344185b2, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sun Sep 09 19:40:32 CST 2018, time=2018-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344184, encodeId=fad034418413, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfBfgWn9nXBgH1sNSiaOAKhsKpN40jDHQKqcRzovau5VibLvREN8uxnu9sKoScBicHSiaDMmbveibFdrBiaD4k4IOPwlG/0, createdBy=b5d11730951, createdName=Jackie Li, createdTime=Sun Sep 09 19:31:44 CST 2018, time=2018-09-09, status=1, ipAttribution=)]
    2018-09-09 1e1b8538m79(暂无匿称)

    不错的文章值得拥有哦

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1930646, encodeId=e170193064672, content=<a href='/topic/show?id=22f61180211' target=_blank style='color:#2F92EE;'>#miR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11802, encryptionId=22f61180211, topicName=miR)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a27288, createdName=smallant2002, createdTime=Thu Jun 06 00:50:00 CST 2019, time=2019-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034043, encodeId=697d2034043bf, content=<a href='/topic/show?id=9613113283e' target=_blank style='color:#2F92EE;'>#MATRix#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11328, encryptionId=9613113283e, topicName=MATRix)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ced3193, createdName=freve, createdTime=Sat Feb 16 09:50:00 CST 2019, time=2019-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767512, encodeId=66341e6751251, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Wed Apr 24 23:50:00 CST 2019, time=2019-04-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918280, encodeId=95441918280f5, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Sat Aug 03 10:50:00 CST 2019, time=2019-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1312353, encodeId=8b4d1312353bb, content=<a href='/topic/show?id=e5571193321' target=_blank style='color:#2F92EE;'>#miRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11933, encryptionId=e5571193321, topicName=miRNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87d405, createdName=Homburg, createdTime=Tue Sep 11 09:50:00 CST 2018, time=2018-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344196, encodeId=8fd93441964c, content=不错的文章值得拥有哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=eff51996281, createdName=1e1b8538m79(暂无匿称), createdTime=Sun Sep 09 21:26:19 CST 2018, time=2018-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344185, encodeId=78d4344185b2, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Sun Sep 09 19:40:32 CST 2018, time=2018-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344184, encodeId=fad034418413, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfBfgWn9nXBgH1sNSiaOAKhsKpN40jDHQKqcRzovau5VibLvREN8uxnu9sKoScBicHSiaDMmbveibFdrBiaD4k4IOPwlG/0, createdBy=b5d11730951, createdName=Jackie Li, createdTime=Sun Sep 09 19:31:44 CST 2018, time=2018-09-09, status=1, ipAttribution=)]
    2018-09-09 医者仁心5538

    学习了

    0

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    2018-09-09 Jackie Li

    学习

    0