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J Biol Chem:活性线粒体通过刺激β-连环蛋白乙酰化来促进成骨分化

2018-09-02 MedSci MedSci原创

骨髓基质(a.k.a.间充质干细胞)细胞(BMSCs)可分化为成骨细胞(OB),脂肪细胞或软骨细胞。当BMSC向OB分化时,它们上调线粒体氧化磷酸化(OxPhos)。在这里,我们研究了将线粒体OxPhos连接到OB分化的机制。首先,我们发现用OxPhos抑制剂治疗BMSC样C3H10T1/2细胞降低了其成骨潜力。有趣的是,ATP水平没有降低,因为糖酵解补偿了OxPhos的减少。因此,线粒体不仅通过

骨髓基质(a.k.a.间充质干细胞)细胞(BMSCs)可分化为成骨细胞(OB),脂肪细胞或软骨细胞。当BMSC向OB分化时,它们上调线粒体氧化磷酸化(OxPhos)。在这里,我们研究了将线粒体OxPhos连接到OB分化的机制。

首先,我们发现用OxPhos抑制剂治疗BMSC样C3H10T1/2细胞降低了其成骨潜力。有趣的是,ATP水平没有降低,因为糖酵解补偿了OxPhos的减少。因此,线粒体不仅通过提供ATP而且通过其他机制支持OB分化。为了揭示这些机制,我们通过用半乳糖取代培养基葡萄糖来刺激C3H10T1/2细胞中的OxPhos,并观察到即使在没有骨诱导剂的情况下,这种取代也增加了OxPhos和骨生成。

β-连环蛋白是成骨中重要的信号传导通路,对OxPhos刺激有反应。通过乙酰化维持β-连环蛋白活性,并且线粒体产生乙酰基供体乙酰-CoA,其在进入Krebs循环后转化为能够离开线粒体的柠檬酸盐。通过ATP柠檬酸裂解酶(ACLY)将胞质柠檬酸转化回乙酰-CoA。我们发现用SB204990(SB)抑制ACLY会逆转半乳糖诱导的β-连环蛋白活性和OB分化。这表明在强制OxPhos刺激后乙酰化涉及β-连环蛋白活化,并且使用免疫沉淀,我们确实检测到SB敏感的β-连环蛋白乙酰化。在骨诱导过程中β-连环蛋白乙酰化和活性均增加,与OxPhos活化同时发生。

综上所述,该研究结果表明活性线粒体通过促进β-连环蛋白乙酰化和活性来支持OB分化。

原始出处:

Shares BH, Busch M, et al., Active mitochondria support osteogenic differentiation by stimulating β-catenin acetylation. J Biol Chem. 2018 Aug 27. pii: jbc.RA118.004102. doi: 10.1074/jbc.RA118.004102.

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    2019-01-13 HinsMax
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    2019-02-09 一叶知秋
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    2018-09-04 zhaojie88
  7. [GetPortalCommentsPageByObjectIdResponse(id=1821335, encodeId=d28d1821335b0, content=<a href='/topic/show?id=428a101612e7' target=_blank style='color:#2F92EE;'>#骨分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101612, encryptionId=428a101612e7, topicName=骨分化)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/qXbLjJB4FSzhQS3C5qQFMJkqicRIJFL6zHFwwhv0I95nzA6xicevQcEica0gk4A58UkbMMriadAgTY2b7N7Yd0ZsQg/132, createdBy=910c2500152, createdName=HinsMax, createdTime=Sun Jan 13 08:50:00 CST 2019, time=2019-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918269, encodeId=c5101918269f4, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Sat Feb 09 08:50:00 CST 2019, time=2019-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956394, encodeId=b0bf1956394f8, 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=80, 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 Aug 07 12:50:00 CST 2019, time=2019-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1767509, encodeId=b3e81e67509c5, content=<a href='/topic/show?id=64f5343e2f' target=_blank style='color:#2F92EE;'>#Biol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3437, encryptionId=64f5343e2f, topicName=Biol)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=446937890434, createdName=12498ebem31暂无昵称, createdTime=Wed Apr 10 10:50:00 CST 2019, time=2019-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1337480, encodeId=9e29133e48016, content=<a href='/topic/show?id=863f5409610' target=_blank style='color:#2F92EE;'>#成骨分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54096, encryptionId=863f5409610, topicName=成骨分化)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqySEUYKeYDjXJMYMrtscBNkpAnLfQZgDcdkEratcJPqS7ARJOXqllZQhCSFicErlBFbIywuoiaP0LQ/132, createdBy=012d2500132, createdName=ms5880526374914242, createdTime=Tue Sep 04 13:50:00 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351807, encodeId=9f3c135180edc, content=<a href='/topic/show?id=e95954093cd' target=_blank style='color:#2F92EE;'>#成骨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54093, encryptionId=e95954093cd, topicName=成骨)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Tue Sep 04 13:50:00 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342329, encodeId=5c243423299c, content=了解一下,谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=115, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Sun Sep 02 23:02:46 CST 2018, time=2018-09-02, status=1, ipAttribution=)]
    2018-09-02 天地飞扬

    了解一下,谢谢分享!

    0

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