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Exp Mol Med：研究发现Cldn11是骨稳态中的新型调节因子

2018-05-18 MedSci MedSci原创

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Claudins（Cldns）是紧密连接（TJs）的成熟组分，在调节细胞旁通透性中起关键作用。一些研究已经探索了Cldn家族成员在骨代谢中的生理方面。然而，中枢神经系统髓鞘主要成分Cldn11对骨稳态的影响尚未见报道。在这项研究中，我们证明Cldn11是一种潜在的骨病治疗靶点，作为骨生成增强和破骨细胞生成抑制的双重调节剂。 我们发现Cldn11在核因子κB配体诱导的破骨细胞（OC）分化和功能

Claudins（Cldns）是紧密连接（TJs）的成熟组分，在调节细胞旁通透性中起关键作用。一些研究已经探索了Cldn家族成员在骨代谢中的生理方面。然而，中枢神经系统髓鞘主要成分Cldn11对骨稳态的影响尚未见报道。在这项研究中，我们证明Cldn11是一种潜在的骨病治疗靶点，作为骨生成增强和破骨细胞生成抑制的双重调节剂。

我们发现Cldn11在核因子κB配体诱导的破骨细胞（OC）分化和功能的受体激活剂中通过下调细胞外信号调节激酶（ERK），布鲁顿酪氨酸激酶和磷脂酶Cγ2的磷酸化而起负作用，反过来在活化的T细胞c1的表达中阻碍c-Fos和核因子。通过Smad1/5/8、ERK和c-Jun氨基末端激酶的磷酸化实现Cldn11的正反馈增强成骨细胞（OB）分化。

重要的是，这种Cldn11依赖性的骨代谢双重事件是由靶向EphrinB2配体反向信号传导和OC中的EphB4受体正向信号传导引起的。与这些体外作用相一致，皮下注射Cldn11重组蛋白在脂多糖诱导的颅骨骨丢失小鼠模型中发挥抗吸收作用，并且在颅骨形成模型中增加成骨活性。

综上所述，这些发现表明Cldn11是骨稳态中的新型调节因子。

原始出处：

Jong Min Baek, Yoon-Hee Cheon, et al., Claudin 11 regulates bone homeostasis via bidirectional EphB4-EphrinB2 signaling. Exp Mol Med. 2018 Apr; 50(4): 50. doi:  10.1038/s12276-018-0076-3

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    2018-08-28 changfy

    #稳态#

    0

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    2019-02-01 liuli5079

    #调节因子#

    0

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    2019-02-05 bugit

    #骨稳态#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1646720, encodeId=cac21646e203a, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Tue Aug 28 00:51:00 CST 2018, time=2018-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969259, encodeId=adba19692599e, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri Feb 01 14:51:00 CST 2019, time=2019-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1993892, encodeId=9881199389203, content=<a href='/topic/show?id=9d59101811e5' target=_blank style='color:#2F92EE;'>#骨稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101811, encryptionId=9d59101811e5, topicName=骨稳态)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=bugit, createdTime=Tue Feb 05 23:51:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1753403, encodeId=dac21e5340397, content=<a href='/topic/show?id=6a57e33772b' target=_blank style='color:#2F92EE;'>#研究发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73377, encryptionId=6a57e33772b, topicName=研究发现)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7e1736602208, createdName=hanhaisha2020, createdTime=Wed Jan 23 06:51:00 CST 2019, time=2019-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=324939, encodeId=953132493971, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=1, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Sun Jun 17 13:34:04 CST 2018, time=2018-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608830, encodeId=e631160883054, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sun May 20 09:51:00 CST 2018, time=2018-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=316378, encodeId=4b5e3163e8d6, content=Claudins(Cldns)是紧密连接(TJs)的成熟组分.在调节细胞旁通透性中起关键作用.一些研究已经探索了Cldn家族成员在骨代谢中的生理方面.然而.中枢神经系统髓鞘主要成分Cldn11对骨稳态的影响尚未见报道.在这项研究中.我们证明Cldn11是一种潜在的骨病治疗靶点.作为骨生成增强和破骨细胞生成抑制的双重调节剂., beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Fri May 18 20:03:35 CST 2018, time=2018-05-18, status=1, ipAttribution=)]
    2019-01-23 hanhaisha2020

    #研究发现#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1646720, encodeId=cac21646e203a, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Tue Aug 28 00:51:00 CST 2018, time=2018-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969259, encodeId=adba19692599e, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri Feb 01 14:51:00 CST 2019, time=2019-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1993892, encodeId=9881199389203, content=<a href='/topic/show?id=9d59101811e5' target=_blank style='color:#2F92EE;'>#骨稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101811, encryptionId=9d59101811e5, topicName=骨稳态)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=bugit, createdTime=Tue Feb 05 23:51:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1753403, encodeId=dac21e5340397, content=<a href='/topic/show?id=6a57e33772b' target=_blank style='color:#2F92EE;'>#研究发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73377, encryptionId=6a57e33772b, topicName=研究发现)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7e1736602208, createdName=hanhaisha2020, createdTime=Wed Jan 23 06:51:00 CST 2019, time=2019-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=324939, encodeId=953132493971, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=1, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Sun Jun 17 13:34:04 CST 2018, time=2018-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608830, encodeId=e631160883054, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sun May 20 09:51:00 CST 2018, time=2018-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=316378, encodeId=4b5e3163e8d6, content=Claudins(Cldns)是紧密连接(TJs)的成熟组分.在调节细胞旁通透性中起关键作用.一些研究已经探索了Cldn家族成员在骨代谢中的生理方面.然而.中枢神经系统髓鞘主要成分Cldn11对骨稳态的影响尚未见报道.在这项研究中.我们证明Cldn11是一种潜在的骨病治疗靶点.作为骨生成增强和破骨细胞生成抑制的双重调节剂., beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Fri May 18 20:03:35 CST 2018, time=2018-05-18, status=1, ipAttribution=)]
    2018-06-17 1e145228m78(暂无匿称)

    学习了.谢谢作者分享!

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1646720, encodeId=cac21646e203a, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Tue Aug 28 00:51:00 CST 2018, time=2018-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969259, encodeId=adba19692599e, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri Feb 01 14:51:00 CST 2019, time=2019-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1993892, encodeId=9881199389203, content=<a href='/topic/show?id=9d59101811e5' target=_blank style='color:#2F92EE;'>#骨稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101811, encryptionId=9d59101811e5, topicName=骨稳态)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=bugit, createdTime=Tue Feb 05 23:51:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1753403, encodeId=dac21e5340397, content=<a href='/topic/show?id=6a57e33772b' target=_blank style='color:#2F92EE;'>#研究发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73377, encryptionId=6a57e33772b, topicName=研究发现)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7e1736602208, createdName=hanhaisha2020, createdTime=Wed Jan 23 06:51:00 CST 2019, time=2019-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=324939, encodeId=953132493971, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=1, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Sun Jun 17 13:34:04 CST 2018, time=2018-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608830, encodeId=e631160883054, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sun May 20 09:51:00 CST 2018, time=2018-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=316378, encodeId=4b5e3163e8d6, content=Claudins(Cldns)是紧密连接(TJs)的成熟组分.在调节细胞旁通透性中起关键作用.一些研究已经探索了Cldn家族成员在骨代谢中的生理方面.然而.中枢神经系统髓鞘主要成分Cldn11对骨稳态的影响尚未见报道.在这项研究中.我们证明Cldn11是一种潜在的骨病治疗靶点.作为骨生成增强和破骨细胞生成抑制的双重调节剂., beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Fri May 18 20:03:35 CST 2018, time=2018-05-18, status=1, ipAttribution=)]
    2018-05-20 ms3994565386320060

    #Med#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1646720, encodeId=cac21646e203a, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Tue Aug 28 00:51:00 CST 2018, time=2018-08-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969259, encodeId=adba19692599e, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Fri Feb 01 14:51:00 CST 2019, time=2019-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1993892, encodeId=9881199389203, content=<a href='/topic/show?id=9d59101811e5' target=_blank style='color:#2F92EE;'>#骨稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101811, encryptionId=9d59101811e5, topicName=骨稳态)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=bugit, createdTime=Tue Feb 05 23:51:00 CST 2019, time=2019-02-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1753403, encodeId=dac21e5340397, content=<a href='/topic/show?id=6a57e33772b' target=_blank style='color:#2F92EE;'>#研究发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73377, encryptionId=6a57e33772b, topicName=研究发现)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7e1736602208, createdName=hanhaisha2020, createdTime=Wed Jan 23 06:51:00 CST 2019, time=2019-01-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=324939, encodeId=953132493971, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=1, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Sun Jun 17 13:34:04 CST 2018, time=2018-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608830, encodeId=e631160883054, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sun May 20 09:51:00 CST 2018, time=2018-05-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=316378, encodeId=4b5e3163e8d6, content=Claudins(Cldns)是紧密连接(TJs)的成熟组分.在调节细胞旁通透性中起关键作用.一些研究已经探索了Cldn家族成员在骨代谢中的生理方面.然而.中枢神经系统髓鞘主要成分Cldn11对骨稳态的影响尚未见报道.在这项研究中.我们证明Cldn11是一种潜在的骨病治疗靶点.作为骨生成增强和破骨细胞生成抑制的双重调节剂., beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7cJ6ejWUr2nIia8qOvAKNdLHr32Df6G8iaoaOx6pHaoiacwp26DaslxZHCGbibZhhCGven4rvmWP60GahtzgFjgCjR/0, createdBy=6b111703011, createdName=有备才能无患, createdTime=Fri May 18 20:03:35 CST 2018, time=2018-05-18, status=1, ipAttribution=)]
    2018-05-18 有备才能无患

    Claudins(Cldns)是紧密连接(TJs)的成熟组分.在调节细胞旁通透性中起关键作用.一些研究已经探索了Cldn家族成员在骨代谢中的生理方面.然而.中枢神经系统髓鞘主要成分Cldn11对骨稳态的影响尚未见报道.在这项研究中.我们证明Cldn11是一种潜在的骨病治疗靶点.作为骨生成增强和破骨细胞生成抑制的双重调节剂.

    0