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J Biol Chem：microRNA-23a簇在成骨细胞分化过程中的功能

2018-10-11 MedSci MedSci原创

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微小RNA（miR）和Hox转录因子在出生后骨形成和体内平衡中具有决定性作用。计算机分析鉴定了HOXA簇mRNA与来自miR-23a簇的微RNA之间的广泛相互作用。然而，miR-23a簇在成骨细胞分化期间的Hox调节仍未定义。我们在前成骨细胞和新型miR-23a簇敲除小鼠模型中进行了探究。 前成骨细胞中miR-23a簇的过表达和敲低分别降低和增加HOXA5，HOXA10和HOXA11蛋白的表

微小RNA（miR）和Hox转录因子在出生后骨形成和体内平衡中具有决定性作用。计算机分析鉴定了HOXA簇mRNA与来自miR-23a簇的微RNA之间的广泛相互作用。然而，miR-23a簇在成骨细胞分化期间的Hox调节仍未定义。我们在前成骨细胞和新型miR-23a簇敲除小鼠模型中进行了探究。

前成骨细胞中miR-23a簇的过表达和敲低分别降低和增加HOXA5，HOXA10和HOXA11蛋白的表达；这些蛋白质的mRNA表现出与miR-23a簇miRNA的明显结合，并且miRNA-3'UTR-报告基因测定证实了抑制。重要的是，在与骨细胞的发育和分化相关的时期中，我们发现HoxA因子与miR-23a簇成员之间的反向表达模式。HOXA5和HOXA11与骨特异性启动子结合，与转录因子RUNX2物理相互作用，并调节骨特异性基因。HOXA5或HOXA11在前成骨细胞中的消耗也减少了细胞分化。

另外，成骨细胞中miR-23a簇的稳定过表达降低了HOXA5和HOXA11向成骨细胞基因启动子的募集，明显抑制组蛋白H3乙酰化。与野生型（WT）小鼠相比，杂合miR-23a簇敲低雌性小鼠（miR-23a ClWT/ZIP）明显增加骨小梁质量。此外，miR-23a簇-这些小鼠的颅骨成骨细胞中的敲低增加了HOXA5和HOXA11的募集，其中启动子组蛋白H3乙酰化显著富集。

总之，这些发现表明miR-23a簇是在成骨过程中维持阶段特异性HoxA因子表达所必需的。

原始出处：

Godfrey TC, Wildman BJ, et al., The microRNA-23a cluster regulates the developmental HoxA cluster function during osteoblast differentiation. J Biol Chem. 2018 Sep 21. pii: jbc.RA118.003052. doi: 10.1074/jbc.RA118.003052.

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    2019-05-19 jiafufeng@yaho

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    #Bio#

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level=null, likeNumber=21, 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 Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495090, encodeId=942814950906b, content=<a href='/topic/show?id=3c0b10182102' target=_blank style='color:#2F92EE;'>#骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101821, encryptionId=3c0b10182102, topicName=骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=723c9147696, createdName=jj000004, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570239, encodeId=d5c915e023902, content=<a href='/topic/show?id=a66ae7809b1' target=_blank style='color:#2F92EE;'>#细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77809, encryptionId=a66ae7809b1, topicName=细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=653c15636865, createdName=karmond, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=349004, encodeId=ecc5349004e0, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Oct 12 08:18:24 CST 2018, time=2018-10-12, status=1, ipAttribution=)]
    2019-08-25 12498ebem31暂无昵称

    #Biol#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1857708, encodeId=e6a4185e7081f, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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=Sun May 19 01:30:00 CST 2019, time=2019-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084449, encodeId=377c208444930, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, 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level=null, likeNumber=21, 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 Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495090, encodeId=942814950906b, content=<a href='/topic/show?id=3c0b10182102' target=_blank style='color:#2F92EE;'>#骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101821, encryptionId=3c0b10182102, topicName=骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=723c9147696, createdName=jj000004, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570239, encodeId=d5c915e023902, content=<a href='/topic/show?id=a66ae7809b1' target=_blank style='color:#2F92EE;'>#细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77809, encryptionId=a66ae7809b1, topicName=细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=653c15636865, createdName=karmond, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=349004, encodeId=ecc5349004e0, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Oct 12 08:18:24 CST 2018, time=2018-10-12, status=1, ipAttribution=)]
    2018-10-13 zhaojie88

    #成骨#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1857708, encodeId=e6a4185e7081f, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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=Sun May 19 01:30:00 CST 2019, time=2019-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084449, encodeId=377c208444930, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, 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topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Sun Aug 25 00:30:00 CST 2019, time=2019-08-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351858, encodeId=637c135185885, content=<a href='/topic/show?id=e95954093cd' target=_blank style='color:#2F92EE;'>#成骨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54093, encryptionId=e95954093cd, topicName=成骨)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435735, encodeId=3a551435e35b3, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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 Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495090, encodeId=942814950906b, content=<a href='/topic/show?id=3c0b10182102' target=_blank style='color:#2F92EE;'>#骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101821, encryptionId=3c0b10182102, topicName=骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=723c9147696, createdName=jj000004, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570239, encodeId=d5c915e023902, content=<a href='/topic/show?id=a66ae7809b1' target=_blank style='color:#2F92EE;'>#细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77809, encryptionId=a66ae7809b1, topicName=细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=653c15636865, createdName=karmond, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=349004, encodeId=ecc5349004e0, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Oct 12 08:18:24 CST 2018, time=2018-10-12, status=1, ipAttribution=)]
    2018-10-13 zhouqu_8

    #microRNA#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1857708, encodeId=e6a4185e7081f, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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=Sun May 19 01:30:00 CST 2019, time=2019-05-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084449, encodeId=377c208444930, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, 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topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Sun Aug 25 00:30:00 CST 2019, time=2019-08-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351858, encodeId=637c135185885, content=<a href='/topic/show?id=e95954093cd' target=_blank style='color:#2F92EE;'>#成骨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54093, encryptionId=e95954093cd, topicName=成骨)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435735, encodeId=3a551435e35b3, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, 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 Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495090, encodeId=942814950906b, content=<a href='/topic/show?id=3c0b10182102' target=_blank style='color:#2F92EE;'>#骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101821, encryptionId=3c0b10182102, topicName=骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=723c9147696, createdName=jj000004, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570239, encodeId=d5c915e023902, content=<a href='/topic/show?id=a66ae7809b1' target=_blank style='color:#2F92EE;'>#细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77809, encryptionId=a66ae7809b1, topicName=细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=653c15636865, createdName=karmond, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=349004, encodeId=ecc5349004e0, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Oct 12 08:18:24 CST 2018, time=2018-10-12, status=1, ipAttribution=)]
    2018-10-13 jj000004

    #骨细胞#

    0

  8. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570239, encodeId=d5c915e023902, content=<a href='/topic/show?id=a66ae7809b1' target=_blank style='color:#2F92EE;'>#细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77809, encryptionId=a66ae7809b1, topicName=细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=653c15636865, createdName=karmond, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=349004, encodeId=ecc5349004e0, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Oct 12 08:18:24 CST 2018, time=2018-10-12, status=1, ipAttribution=)]
    2018-10-13 karmond

    #细胞分化#

    0

  9. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570239, encodeId=d5c915e023902, content=<a href='/topic/show?id=a66ae7809b1' target=_blank style='color:#2F92EE;'>#细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77809, encryptionId=a66ae7809b1, topicName=细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=653c15636865, createdName=karmond, createdTime=Sat Oct 13 14:30:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=349004, encodeId=ecc5349004e0, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Fri Oct 12 08:18:24 CST 2018, time=2018-10-12, status=1, ipAttribution=)]
    2018-10-12 kafei

    学习了谢谢

    0