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Bone Res：NUMB通过泛素化促进PTEN和GLI1的降解来维持骨量

2018-11-22 MedSci MedSci原创

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衔接蛋白NUMB参与不对称分裂和细胞的转化，并被认为是Notch的拮抗剂。 既往研究已经证明成骨细胞中的Notch活化有助于高骨量。然而，在这项研究中，在使用成骨细胞特异性Col1a1-2.3-Cre消融Numb及其同源物Numbl的9周龄小鼠中发现了骨质减少的表型。骨小梁质量急剧下降，而皮质骨质量未受影响。在这里，Notch信号未被激活，而在人染色体10（PTEN）上缺失的张力蛋白同源物（

衔接蛋白NUMB参与不对称分裂和细胞的转化，并被认为是Notch的拮抗剂。

既往研究已经证明成骨细胞中的Notch活化有助于高骨量。然而，在这项研究中，在使用成骨细胞特异性Col1a1-2.3-Cre消融Numb及其同源物Numbl的9周龄小鼠中发现了骨质减少的表型。骨小梁质量急剧下降，而皮质骨质量未受影响。在这里，Notch信号未被激活，而在人染色体10（PTEN）上缺失的张力蛋白同源物（其使磷脂酰肌醇3-激酶去磷酸化）升高，减弱蛋白激酶B（Akt）。泛素化测定揭示，在存在神经前体细胞表达的发育上调节的蛋白4-1的情况下，NUMB可在生理上促进PTEN泛素化。此外，Numb/Numbl的缺乏也通过GLI1激活了Hedgehog通路。该过程可改善核因子-kB配体的受体活化剂与骨保护素的比例，增强了破骨细胞的分化和骨吸收。

综上所述，该研究而为NUMB和NUMBL骨骼稳态的新功能提供了新的见解。

原始出处：

Ling Ye, Feng Lou, et al., NUMB maintains bone mass by promoting degradation of PTEN and GLI1 via ubiquitination in osteoblasts. Bone Res. 2018; 6: 32.

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    2018-11-24 clmlylxy

    #骨量#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1667177, encodeId=4963166e177c6, content=<a href='/topic/show?id=8863101899aa' target=_blank style='color:#2F92EE;'>#骨量#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101899, encryptionId=8863101899aa, topicName=骨量)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=35f026117353, createdName=clmlylxy, createdTime=Sat Nov 24 10:59:00 CST 2018, time=2018-11-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1915194, encodeId=efc71915194f3, content=<a href='/topic/show?id=05343619cf' target=_blank style='color:#2F92EE;'>#Bone#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3619, encryptionId=05343619cf, topicName=Bone)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7dc7399, createdName=apoenzyme, createdTime=Tue Apr 02 03:59:00 CST 2019, time=2019-04-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1315927, encodeId=cd4f131592ef0, content=<a href='/topic/show?id=134f14834f2' target=_blank style='color:#2F92EE;'>#PTEN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14834, encryptionId=134f14834f2, topicName=PTEN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f67438, createdName=xiaogang317, createdTime=Fri Nov 23 15:59:00 CST 2018, time=2018-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353425, encodeId=cf0b353425f3, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, 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 Nov 23 07:55:39 CST 2018, time=2018-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353309, encodeId=21d73533099f, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6d551998554, createdName=1e1c07bdm01(暂无匿称), createdTime=Thu Nov 22 06:06:23 CST 2018, time=2018-11-22, status=1, ipAttribution=)]
    2019-04-02 apoenzyme

    #Bone#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1667177, encodeId=4963166e177c6, content=<a href='/topic/show?id=8863101899aa' target=_blank style='color:#2F92EE;'>#骨量#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101899, encryptionId=8863101899aa, topicName=骨量)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=35f026117353, createdName=clmlylxy, createdTime=Sat Nov 24 10:59:00 CST 2018, time=2018-11-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1915194, encodeId=efc71915194f3, content=<a href='/topic/show?id=05343619cf' target=_blank style='color:#2F92EE;'>#Bone#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3619, encryptionId=05343619cf, topicName=Bone)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7dc7399, createdName=apoenzyme, createdTime=Tue Apr 02 03:59:00 CST 2019, time=2019-04-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1315927, encodeId=cd4f131592ef0, content=<a href='/topic/show?id=134f14834f2' target=_blank style='color:#2F92EE;'>#PTEN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14834, encryptionId=134f14834f2, topicName=PTEN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f67438, createdName=xiaogang317, createdTime=Fri Nov 23 15:59:00 CST 2018, time=2018-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353425, encodeId=cf0b353425f3, content=学习了谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, 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 Nov 23 07:55:39 CST 2018, time=2018-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=353309, encodeId=21d73533099f, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6d551998554, createdName=1e1c07bdm01(暂无匿称), createdTime=Thu Nov 22 06:06:23 CST 2018, time=2018-11-22, status=1, ipAttribution=)]
    2018-11-23 xiaogang317

    #PTEN#

    0

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    2018-11-23 kafei

    学习了谢谢

    0

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    2018-11-22 1e1c07bdm01(暂无匿称)

    好

    0