Cell Physiol Biochem:分化型破骨细胞中β-Catenin的组成性激活诱导小鼠骨丢失

2018-11-09 MedSci MedSci原创

Wnt/β-连环蛋白信号传导通路的激活已经在骨生物学中被广泛研究并且显示出促进骨形成。然而,其对破骨细胞分化的特定作用尚未完全阐明。本研究旨在确定β-连环蛋白在破骨细胞生成和骨稳态中的作用。 在本研究中,编码磷酸化靶标丝氨酸/苏氨酸残基的β-连环蛋白基因(Ctnnb1)等位基因中的外显子3侧翼为floxP序列。将Ctnnb1flox(外显子3)/ flox(外显子3)小鼠与破骨细胞特异性Ct

Wnt/β-连环蛋白信号传导通路的激活已经在骨生物学中被广泛研究并且显示出促进骨形成。然而,其对破骨细胞分化的特定作用尚未完全阐明。本研究旨在确定β-连环蛋白在破骨细胞生成和骨稳态中的作用。

在本研究中,编码磷酸化靶标丝氨酸/苏氨酸残基的β-连环蛋白基因(Ctnnb1)等位基因中的外显子3侧翼为floxP序列。将Ctnnb1flox(外显子3)/ flox(外显子3)小鼠与破骨细胞特异性Ctsk-Cre小鼠杂交,产生表现出条件β-连环蛋白活化的小鼠(Ctsk-Cre; Ctnnb1flox(外显子3)/ +,命名为CA-β-连环蛋白)。通过微型计算机断层扫描(micro-CT)和组织形态学分析骨生长和骨量。为了进一步检查破骨细胞活性,从体外分离自CA-β-连环蛋白和对照小鼠的骨髓单核细胞(BMM)诱导破骨细胞。通过抗酒石酸酸性磷酸酶(TRAP)染色,免疫荧光染色和逆转录定量PCR(RT-qPCR)分析检测破骨细胞分化。

结果显示,在CA-β-连环蛋白小鼠中观察到生长迟缓和低骨量。与对照相比,CA-β-catenin小鼠在生长板下以及更薄的皮质骨中骨小梁的数量显著减少。此外,在CA-β-catenin小鼠的小梁骨和皮质骨表面观察到TRAP阳性破骨细胞增多;在体外观察到一致的结果。在CA-β-连环蛋白组中,从BMM诱导过量的破骨细胞,伴随着破骨细胞相关标记基因的表达增加。

综上所述,这些结果表明破骨细胞中β-连环蛋白的组成型活化促进破骨细胞形成,导致骨质流失。

原始出处:

Sui X, Deng S, et al., Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice. Cell Physiol Biochem. 2018;48(5):2091-2102. doi: 10.1159/000492549. Epub 2018 Aug 14.

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    2019-08-01 维他命
  3. 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    2018-12-06 sunylz
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  5. 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  6. 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  7. 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  8. 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topicName=Physio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Sat Apr 20 15:49:00 CST 2019, time=2019-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870981, encodeId=90b818e098191, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Jan 26 20:49:00 CST 2019, time=2019-01-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1309995, encodeId=6a60130999555, 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, 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objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6d551998554, createdName=1e1c07bdm01(暂无匿称), createdTime=Sun Nov 11 07:03:06 CST 2018, time=2018-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352100, encodeId=025735210054, content=谢谢了,学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=30331616752, createdName=txqjm, createdTime=Sat Nov 10 06:33:17 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352071, encodeId=46e23520e110, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Fri Nov 09 22:57:58 CST 2018, time=2018-11-09, status=1, ipAttribution=)]
  9. [GetPortalCommentsPageByObjectIdResponse(id=1991237, encodeId=a77e199123eb0, content=<a href='/topic/show?id=0e971015e4bd' target=_blank style='color:#2F92EE;'>#骨丢失#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101574, encryptionId=0e971015e4bd, topicName=骨丢失)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Mon Apr 08 04:49:00 CST 2019, time=2019-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1961254, encodeId=322b196125401, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, 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objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6d551998554, createdName=1e1c07bdm01(暂无匿称), createdTime=Sun Nov 11 07:03:06 CST 2018, time=2018-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352100, encodeId=025735210054, content=谢谢了,学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=30331616752, createdName=txqjm, createdTime=Sat Nov 10 06:33:17 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352071, encodeId=46e23520e110, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Fri Nov 09 22:57:58 CST 2018, time=2018-11-09, status=1, ipAttribution=)]
    2018-11-10 txqjm

    谢谢了,学习

    0

  10. 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objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6d551998554, createdName=1e1c07bdm01(暂无匿称), createdTime=Sun Nov 11 07:03:06 CST 2018, time=2018-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352100, encodeId=025735210054, content=谢谢了,学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=30331616752, createdName=txqjm, createdTime=Sat Nov 10 06:33:17 CST 2018, time=2018-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=352071, encodeId=46e23520e110, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Fri Nov 09 22:57:58 CST 2018, time=2018-11-09, status=1, ipAttribution=)]
    2018-11-09 医者仁心5538

    学习了

    0