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Toxicol Sci：AhR在人间充质干细胞分化中的作用研究

2018-09-12 MedSci MedSci原创

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多能间充质干细胞保持分化成脂肪形成，软骨形成或成骨细胞谱系的能力。越来越多的人担心暴露于环境因子如芳烃受体（AhR）配体可能扰乱负责正常骨形成的成骨通路。本研究旨在评估原型AhR配体2,3,7,8-四氯二苯并二恶英（TCDD）在体外破坏人骨衍生间充质干细胞（hBMSCs）成骨分化的潜力。 将来自三个供体的原代hBMSC暴露于10nM TCDD，并使用选择的成骨组织学，生物化学和转录标记物来鉴

多能间充质干细胞保持分化成脂肪形成，软骨形成或成骨细胞谱系的能力。越来越多的人担心暴露于环境因子如芳烃受体（AhR）配体可能扰乱负责正常骨形成的成骨通路。本研究旨在评估原型AhR配体2,3,7,8-四氯二苯并二恶英（TCDD）在体外破坏人骨衍生间充质干细胞（hBMSCs）成骨分化的潜力。

将来自三个供体的原代hBMSC暴露于10nM TCDD，并使用选择的成骨组织学，生物化学和转录标记物来鉴定分化。结果显示，暴露于10nM TCDD导致初级hBMSCs分化的末期阶段碱性磷酸酶（ALP）活性和基质矿化的减弱。在转录水平，转录调节因子DLX5和其他成骨标志物（ALP，OPN和IBSP）的表达减弱；相反，FGF9和FGF18的表达上调。干细胞效能标志物SOX2，NANOG和SALL4的表达在成骨对照中降低，而在TCDD处理的细胞中的表达与未分化细胞的表达类似。与AhR拮抗剂GNF351共暴露后可阻断TCDD介导的基质矿化的减弱，且完全或部分拯救与成骨调节、ECM和/或维持多能性相关的基因的表达。

因此，该研究结果表明，AhR反式激活可减弱多潜能hBMSCs的成骨细胞分化。该研究还强调了使用原代人MSCs来评估体外化学和药物制剂的骨诱导或骨毒性潜力。

原始出处：

Watson ATD, Nordberg RC, et al., Experimental evidence for an inhibitory role of AhR activation in human mesenchymal stem cell differentiation. Toxicol Sci. 2018 Sep 7. doi: 10.1093/toxsci/kfy225.

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    2018-10-13 h.y200607_23674418

    #间充质干细#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1815370, encodeId=be3918153e0e8, content=<a href='/topic/show?id=ae359e231d4' target=_blank style='color:#2F92EE;'>#间充质干细#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97231, encryptionId=ae359e231d4, topicName=间充质干细)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b632500090, createdName=h.y200607_23674418, createdTime=Sat Oct 13 09:59:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570230, encodeId=c9c315e0230fc, 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=30, 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=Fri Sep 14 11:59:00 CST 2018, time=2018-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344732, encodeId=4151344e3274, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Wed Sep 12 22:27:21 CST 2018, time=2018-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344722, encodeId=bbd7344e22df, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Sep 12 21:46:57 CST 2018, time=2018-09-12, status=1, ipAttribution=)]
    2018-09-14 karmond

    #细胞分化#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1815370, encodeId=be3918153e0e8, content=<a href='/topic/show?id=ae359e231d4' target=_blank style='color:#2F92EE;'>#间充质干细#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97231, encryptionId=ae359e231d4, topicName=间充质干细)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b632500090, createdName=h.y200607_23674418, createdTime=Sat Oct 13 09:59:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570230, encodeId=c9c315e0230fc, 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=30, 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=Fri Sep 14 11:59:00 CST 2018, time=2018-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344732, encodeId=4151344e3274, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Wed Sep 12 22:27:21 CST 2018, time=2018-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344722, encodeId=bbd7344e22df, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Sep 12 21:46:57 CST 2018, time=2018-09-12, status=1, ipAttribution=)]
    2018-09-12 医者仁心5538

    学习了

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1815370, encodeId=be3918153e0e8, content=<a href='/topic/show?id=ae359e231d4' target=_blank style='color:#2F92EE;'>#间充质干细#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97231, encryptionId=ae359e231d4, topicName=间充质干细)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b632500090, createdName=h.y200607_23674418, createdTime=Sat Oct 13 09:59:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570230, encodeId=c9c315e0230fc, 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=30, 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=Fri Sep 14 11:59:00 CST 2018, time=2018-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344732, encodeId=4151344e3274, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Wed Sep 12 22:27:21 CST 2018, time=2018-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=344722, encodeId=bbd7344e22df, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Wed Sep 12 21:46:57 CST 2018, time=2018-09-12, status=1, ipAttribution=)]
    2018-09-12 明月清辉

    谢谢分享，学习了

    0

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