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Stem Cell Res Ther：Azoramide通过抑制GLP-1受体-PKA-β-连环蛋白途径来促进脂肪生成以抵抗骨生成

2018-03-13 MedSci MedSci原创

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间充质干细胞（MSCs）对骨或脂肪细胞的作用由Wnt相关信号传导和胰高血糖素样肽-1受体（GLP-1R）决定。据报道，内质网应激缓解剂Azoramide具有抗糖尿病作用。在这项研究中，我们调查了azoramide在调节MSCs的成脂或成骨分化中的功能。 在这项研究中，使用微型计算机断层扫描和组织学分析骨形态发生蛋白（BMP）2诱导的壁骨膜骨形成，C3H10T1/2和小鼠骨髓MSC衍生的骨形成；脂肪

间充质干细胞（MSCs）对骨或脂肪细胞的作用由Wnt相关信号传导和胰高血糖素样肽-1受体（GLP-1R）决定。据报道，内质网应激缓解剂Azoramide具有抗糖尿病作用。在这项研究中，我们调查了azoramide在调节MSCs的成脂或成骨分化中的功能。

在这项研究中，使用微型计算机断层扫描和组织学分析骨形态发生蛋白（BMP）2诱导的壁骨膜骨形成，C3H10T1/2和小鼠骨髓MSC衍生的骨形成；脂肪形成及骨组织和脂滴的特异性染色用于评估azoramide在MSC分化中的作用。收集细胞进行Western印迹和定量实时聚合酶链反应（PCR），并用免疫荧光染色来研究Azoramide调节MSC分化的潜在机制。

MSC来源的骨形成测定法显示，偶氮酰胺处理细胞命运决定能力有利于脂肪形成而不是骨形成。进一步的机制表征揭示，GLP-1R激动剂肽exendin-4（Ex-4）和GLP-1R小干扰（si）RNA都消除了偶氮酰胺双重作用。此外，cAMP-蛋白激酶A（PKA）介导的核β-连环蛋白活性负责azoramide对骨形成的负面作用，有利于脂肪生成。

综上所述，该研究结果表明，在MSC谱系测定中，偶氮酰胺可以作为抗GLP-1R的拮抗剂。

原始出处：

Ruan B, Zhu Z, et al., Azoramide, a novel regulator, favors adipogenesis against osteogenesis through inhibiting the GLP-1 receptor-PKA-β-catenin pathway. Stem Cell Res Ther. 2018 Mar 9;9(1):57. doi: 10.1186/s13287-018-0771-y.

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    2018-10-17 zhaozhouchifen

    #Cell#

    0

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    2018-10-13 hb2008ye

    #stem cell#

    0

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    2018-11-30 12498e5fm22(暂无昵称)

    #AZ#

    0

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    2018-05-23 ms7899726347904398

    #β-连环蛋白#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1870497, encodeId=565c18e049735, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Oct 17 14:08:00 CST 2018, time=2018-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1794566, encodeId=c1451e945667b, content=<a href='/topic/show?id=82b416e79f5' target=_blank style='color:#2F92EE;'>#stem cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16779, encryptionId=82b416e79f5, topicName=stem cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Sat Oct 13 18:08:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1714769, encodeId=9d461e1476933, content=<a href='/topic/show?id=021230e312' target=_blank style='color:#2F92EE;'>#AZ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=14, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3073, encryptionId=021230e312, topicName=AZ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e5031899089, createdName=12498e5fm22(暂无昵称), createdTime=Fri Nov 30 23:08:00 CST 2018, time=2018-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956387, encodeId=05e0195638e29, content=<a href='/topic/show?id=eafb192048e' target=_blank style='color:#2F92EE;'>#β-连环蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19204, encryptionId=eafb192048e, topicName=β-连环蛋白)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/2898B09F0DA89357D0D54A725E611AC7/100, createdBy=fdd32500040, createdName=ms7899726347904398, createdTime=Wed May 23 18:08:00 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1960765, encodeId=efb51960e65d6, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=14, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sun Jul 08 03:08:00 CST 2018, time=2018-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422721, encodeId=c89d1422e2187, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Thu Mar 15 12:08:00 CST 2018, time=2018-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482103, encodeId=d071148210354, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu Mar 15 12:08:00 CST 2018, time=2018-03-15, status=1, ipAttribution=)]
    2018-07-08 柳叶一刀

    #CEL#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1870497, encodeId=565c18e049735, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Oct 17 14:08:00 CST 2018, time=2018-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1794566, encodeId=c1451e945667b, content=<a href='/topic/show?id=82b416e79f5' target=_blank style='color:#2F92EE;'>#stem cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16779, encryptionId=82b416e79f5, topicName=stem cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Sat Oct 13 18:08:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1714769, encodeId=9d461e1476933, content=<a href='/topic/show?id=021230e312' target=_blank style='color:#2F92EE;'>#AZ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=14, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3073, encryptionId=021230e312, topicName=AZ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e5031899089, createdName=12498e5fm22(暂无昵称), createdTime=Fri Nov 30 23:08:00 CST 2018, time=2018-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956387, encodeId=05e0195638e29, content=<a href='/topic/show?id=eafb192048e' target=_blank style='color:#2F92EE;'>#β-连环蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19204, encryptionId=eafb192048e, topicName=β-连环蛋白)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/2898B09F0DA89357D0D54A725E611AC7/100, createdBy=fdd32500040, createdName=ms7899726347904398, createdTime=Wed May 23 18:08:00 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1960765, encodeId=efb51960e65d6, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=14, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sun Jul 08 03:08:00 CST 2018, time=2018-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422721, encodeId=c89d1422e2187, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Thu Mar 15 12:08:00 CST 2018, time=2018-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482103, encodeId=d071148210354, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu Mar 15 12:08:00 CST 2018, time=2018-03-15, status=1, ipAttribution=)]
    2018-03-15 yibei

    #GLP-1#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1870497, encodeId=565c18e049735, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Oct 17 14:08:00 CST 2018, time=2018-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1794566, encodeId=c1451e945667b, content=<a href='/topic/show?id=82b416e79f5' target=_blank style='color:#2F92EE;'>#stem cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16779, encryptionId=82b416e79f5, topicName=stem cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Sat Oct 13 18:08:00 CST 2018, time=2018-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1714769, encodeId=9d461e1476933, content=<a href='/topic/show?id=021230e312' target=_blank style='color:#2F92EE;'>#AZ#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=14, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3073, encryptionId=021230e312, topicName=AZ)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e5031899089, createdName=12498e5fm22(暂无昵称), createdTime=Fri Nov 30 23:08:00 CST 2018, time=2018-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956387, encodeId=05e0195638e29, content=<a href='/topic/show?id=eafb192048e' target=_blank style='color:#2F92EE;'>#β-连环蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19204, encryptionId=eafb192048e, topicName=β-连环蛋白)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/2898B09F0DA89357D0D54A725E611AC7/100, createdBy=fdd32500040, createdName=ms7899726347904398, createdTime=Wed May 23 18:08:00 CST 2018, time=2018-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1960765, encodeId=efb51960e65d6, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=14, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=778d36, createdName=柳叶一刀, createdTime=Sun Jul 08 03:08:00 CST 2018, time=2018-07-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422721, encodeId=c89d1422e2187, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Thu Mar 15 12:08:00 CST 2018, time=2018-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482103, encodeId=d071148210354, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu Mar 15 12:08:00 CST 2018, time=2018-03-15, status=1, ipAttribution=)]
    2018-03-15 12498bb3m92(暂无昵称)

    #STEM#

    0