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Open Biol:骨细胞TSC1促进硬化蛋白分泌以抑制小鼠的骨生成

2019-05-25 不详 网络

骨细胞分泌糖蛋白硬化蛋白以抑制成骨细胞的骨形成,但是骨细胞中硬化蛋白的产生是如何被调节的仍然不清楚。在这里,我们显示骨细胞中的结节性硬化症复合物1(TSC1)通过抑制雷帕霉素复合物1(mTORC1)的机制目标和下调Sirt1来促进硬化蛋白分泌。我们生成了具有DMP1-Cre指导的Tsc1基因缺失(Tsc1 CKO)的小鼠,以组成型激活骨细胞中的mTORC1。尽管骨细胞TSC1破坏增加了RANKL表

骨细胞分泌糖蛋白硬化蛋白以抑制成骨细胞的骨形成,但是骨细胞中硬化蛋白的产生是如何被调节的仍然不清楚。在这里,我们显示骨细胞中的结节性硬化症复合物1(TSC1)通过抑制雷帕霉素复合物1(mTORC1)的机制目标和下调Sirt1来促进硬化蛋白分泌。

我们生成了具有DMP1-Cre指导的Tsc1基因缺失(Tsc1 CKO)的小鼠,以组成型激活骨细胞中的mTORC1。尽管骨细胞TSC1破坏增加了RANKL表达和破骨细胞形成,但它明显降低了骨中硬化蛋白的产生,导致严重的骨硬化并增强了小鼠的骨形成。敲除TSC1激活mTORC1并减少硬化蛋白,而雷帕霉素抑制mTORC1并增加MLO-Y4骨细胞样细胞中的硬化蛋白mRNA和蛋白表达水平。此外,机械加载激活mTORC1并防止骨细胞中的硬化蛋白表达。在机制上,TSC1通过抑制mTORC1和下调Sirt1(scerostin基因Sost的抑制因子)来促进硬化蛋白的产生并预防骨生成。

总之,该研究结果揭示了TSC1 / mTORC1信号传导在体外机械负荷响应中调节骨细胞硬化蛋白分泌和骨形成中的作用。靶向TSC1代表了增加骨生成和预防骨丢失相关疾病的潜在策略。

原始出处:

Liu W, Wang Z, et al., Osteocyte TSC1 promotes sclerostin secretion to restrain osteogenesis in mice. Open Biol. 2019 May 31;9(5):180262. doi: 10.1098/rsob.180262.

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    2020-04-16 sunylz
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    2019-12-16 feather89
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    2019-06-27 gwc392
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    2019-06-12 柳叶一刀
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  6. [GetPortalCommentsPageByObjectIdResponse(id=1918710, encodeId=28c91918e10f4, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Thu Apr 16 18:19:00 CST 2020, time=2020-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1727993, encodeId=932e1e2799376, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f06c33759375, createdName=feather89, createdTime=Mon Dec 16 05:19:00 CST 2019, time=2019-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682526, encodeId=c9661682526c8, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Thu Jun 27 09:19:00 CST 2019, time=2019-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767657, encodeId=b4831e67657ae, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Wed Jun 12 05:19:00 CST 2019, time=2019-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495170, encodeId=cdec14951e0ac, 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=71, 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=Mon May 27 13:19:00 CST 2019, time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366845, encodeId=651636684574, content=好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Mon May 27 06:10:20 CST 2019, time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366782, encodeId=696b366e82e1, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Sat May 25 23:25:09 CST 2019, time=2019-05-25, status=1, ipAttribution=)]
    2019-05-27 yjs木玉

    好好好好好好

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1918710, encodeId=28c91918e10f4, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Thu Apr 16 18:19:00 CST 2020, time=2020-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1727993, encodeId=932e1e2799376, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f06c33759375, createdName=feather89, createdTime=Mon Dec 16 05:19:00 CST 2019, time=2019-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1682526, encodeId=c9661682526c8, content=<a href='/topic/show?id=d4d031e8074' target=_blank style='color:#2F92EE;'>#分泌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31780, encryptionId=d4d031e8074, topicName=分泌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0da227938338, createdName=gwc392, createdTime=Thu Jun 27 09:19:00 CST 2019, time=2019-06-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767657, encodeId=b4831e67657ae, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Wed Jun 12 05:19:00 CST 2019, time=2019-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1495170, encodeId=cdec14951e0ac, 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=71, 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=Mon May 27 13:19:00 CST 2019, time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366845, encodeId=651636684574, content=好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Mon May 27 06:10:20 CST 2019, time=2019-05-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366782, encodeId=696b366e82e1, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0aa31415219, createdName=orangesking, createdTime=Sat May 25 23:25:09 CST 2019, time=2019-05-25, status=1, ipAttribution=)]
    2019-05-25 orangesking

    0

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