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Cell Death Dis:eIF2α信号参与调节成骨细胞和破骨细胞的平衡

2019-12-22 QQY MedSci原创

绝经后骨质疏松症的骨流失主要是由于骨形成相关成骨细胞和骨吸收相关破骨细胞的失衡所引起的。 Salubrinal是一种合成的化合物,可选择性抑制eIF2α(真核翻译起始因子2α)的去磷酸化。 eIF2α磷酸化可减轻内质网(ER)应激作用,进而可能会激活细胞的自噬作用。在本研究中,研究人员推测eIF2α信号可以通过促进成骨细胞的自噬和抑制破骨细胞的发育来调节骨内稳态。为了验证这一推测,研究人员使用sa

绝经后骨质疏松症的骨流失主要是由于骨形成相关成骨细胞和骨吸收相关破骨细胞的失衡所引起的。 Salubrinal是一种合成的化合物,可选择性抑制eIF2α(真核翻译起始因子2α)的去磷酸化。 eIF2α磷酸化可减轻内质网(ER)应激作用,进而可能会激活细胞的自噬作用。

在本研究中,研究人员推测eIF2α信号可以通过促进成骨细胞的自噬和抑制破骨细胞的发育来调节骨内稳态。为了验证这一推测,研究人员使用salubrinal化合物来增强卵巢切除(OVX)小鼠模型和体外培养细胞的eIF2α磷酸化水平。

在OVX模型中,salubinal可以防止粗面内质网的异常扩张,并可减少酸性囊泡的数量。salubinal可调节内质网应激相关信号分子,如Bip,p-eIF2α,ATF4和CHOP,并可通过调节eIF2α,Atg7,LC3和p62促进成骨细胞的自噬。 Salubrinal可以显著缓解OVX所引起的症状,如骨矿物质密度和骨体积分数的降低。 Salubrinal还可通过抑制NFATc1(活化T细胞质1核因子)来促进原代骨髓衍生的成骨细胞的分化并减少相应的破骨细胞的形成。活细胞成像和RNA干扰显示,Rac1 GTPase参与抑制破骨细胞的形成。

综上所述,本研究表明内质网应激-细胞自噬这条途径在OVX小鼠中起着重要作用,而维持eIF2α的磷酸化可以修复骨形成相关的成骨细胞,抑制NFATc1和Rac1 GTPase则可调节骨吸收相关的破骨细胞。

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    2020-06-12 维他命
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    2020-04-02 cmj8wellington
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  6. [GetPortalCommentsPageByObjectIdResponse(id=1871527, encodeId=d28c18e152715, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Thu Jul 16 18:26:00 CST 2020, time=2020-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961818, encodeId=f907196181860, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Jun 12 06:26:00 CST 2020, time=2020-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013128, encodeId=7040201312821, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Thu Apr 02 06:26:00 CST 2020, time=2020-04-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785147, encodeId=80201e851474e, content=<a href='/topic/show?id=96a9662eec' target=_blank style='color:#2F92EE;'>#eIF2α#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6627, encryptionId=96a9662eec, topicName=eIF2α)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/L2dMhrxjvSWuPWKZZP1I83Rw21EWia7LVTYJibLQkb4oTibrYLwhnAXntTBWR3FruIzKfNMiaBwhYV0AKNmiaNxfialg/132, createdBy=6ea92500119, createdName=ms9608593228839890, createdTime=Sun May 03 20:26:00 CST 2020, time=2020-05-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1310011, encodeId=1e1b131001177, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352225, encodeId=deda1352225ef, content=<a href='/topic/show?id=e95954093cd' target=_blank style='color:#2F92EE;'>#成骨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, 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=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495181, encodeId=28291495181fa, 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=67, 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=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531499, encodeId=668815314994c, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=)]
    2019-12-24 zhaojie88
  7. [GetPortalCommentsPageByObjectIdResponse(id=1871527, encodeId=d28c18e152715, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Thu Jul 16 18:26:00 CST 2020, time=2020-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961818, encodeId=f907196181860, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Jun 12 06:26:00 CST 2020, time=2020-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013128, encodeId=7040201312821, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Thu Apr 02 06:26:00 CST 2020, time=2020-04-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785147, encodeId=80201e851474e, content=<a href='/topic/show?id=96a9662eec' target=_blank style='color:#2F92EE;'>#eIF2α#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6627, encryptionId=96a9662eec, topicName=eIF2α)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/L2dMhrxjvSWuPWKZZP1I83Rw21EWia7LVTYJibLQkb4oTibrYLwhnAXntTBWR3FruIzKfNMiaBwhYV0AKNmiaNxfialg/132, createdBy=6ea92500119, createdName=ms9608593228839890, createdTime=Sun May 03 20:26:00 CST 2020, time=2020-05-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1310011, encodeId=1e1b131001177, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352225, encodeId=deda1352225ef, content=<a href='/topic/show?id=e95954093cd' target=_blank style='color:#2F92EE;'>#成骨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, 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=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495181, encodeId=28291495181fa, 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=67, 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=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531499, encodeId=668815314994c, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1871527, encodeId=d28c18e152715, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Thu Jul 16 18:26:00 CST 2020, time=2020-07-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961818, encodeId=f907196181860, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Jun 12 06:26:00 CST 2020, time=2020-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013128, encodeId=7040201312821, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Thu Apr 02 06:26:00 CST 2020, time=2020-04-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785147, encodeId=80201e851474e, content=<a href='/topic/show?id=96a9662eec' target=_blank style='color:#2F92EE;'>#eIF2α#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6627, encryptionId=96a9662eec, topicName=eIF2α)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/L2dMhrxjvSWuPWKZZP1I83Rw21EWia7LVTYJibLQkb4oTibrYLwhnAXntTBWR3FruIzKfNMiaBwhYV0AKNmiaNxfialg/132, createdBy=6ea92500119, createdName=ms9608593228839890, createdTime=Sun May 03 20:26:00 CST 2020, time=2020-05-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1310011, encodeId=1e1b131001177, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352225, encodeId=deda1352225ef, content=<a href='/topic/show?id=e95954093cd' target=_blank style='color:#2F92EE;'>#成骨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, 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=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495181, encodeId=28291495181fa, 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=67, 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=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531499, encodeId=668815314994c, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Tue Dec 24 06:26:00 CST 2019, time=2019-12-24, status=1, ipAttribution=)]
    2019-12-24 cy0328
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