Cell Death Dis:伴侣蛋白60维持成骨细胞自噬并通过RPTOR抵消糖皮质激素加重骨质疏松症

2018-09-24 MedSci MedSci原创

糖皮质激素过量的药物会打破成骨细胞的体内平衡,并加剧骨量和微观结构的丧失,从而加速骨质疏松症的发生。研究发现热休克蛋白60(HSP60)可在遇到有害应激时维持细胞微环境中的蛋白质功能。 在这项研究中,我们发现超生理性地塞米松可降低成骨细胞培养物中HSP60的表达以及失调的自噬。HSP60需要维持自噬标记Atg4,Atg12表达,LC3-II转换和自噬斑点形成,并减轻糖皮质激素诱导的成骨基因表

糖皮质激素过量的药物会打破成骨细胞的体内平衡,并加剧骨量和微观结构的丧失,从而加速骨质疏松症的发生。研究发现热休克蛋白60(HSP60)可在遇到有害应激时维持细胞微环境中的蛋白质功能。

在这项研究中,我们发现超生理性地塞米松可降低成骨细胞培养物中HSP60的表达以及失调的自噬。HSP60需要维持自噬标记Atg4,Atg12表达,LC3-II转换和自噬斑点形成,并减轻糖皮质激素诱导的成骨基因表达缺失和矿化基质积累。mTOR复合物1(RPTOR)的调节因子相关蛋白存在于HSP60免疫沉淀物中,有助于HSP60促进的自噬和成骨,因为敲低RPTOR损害自噬流入和成骨活性。HSP60通过减少糖皮质激素诱导的RPTOR去磷酸化,聚集和泛素化来屏蔽RPTOR功能障碍。

在体内,强制性RPTOR表达可减弱甲基强的松龙诱导的小鼠成骨细胞自噬、骨量和小梁微结构的丧失。与野生型小鼠相比,HSP60转基因小鼠的皮质骨及矿物质增加,成骨细胞增殖以及骨髓间充质细胞的更高成骨。HSP60过表达保留了RPTOR信号传导,持续成骨细胞自噬,并且损害了糖皮质激素诱导的骨丢失和稀疏的小梁组织病理学的严重性。

总之,HSP60对维持成骨细胞自噬至关重要,这有利于矿化基质的产生。它通过将RPTOR作用稳定到自噬来抵御糖皮质激素诱导的成骨细胞凋亡和骨丢失。该研究为伴侣蛋白保护免受糖皮质激素诱导的成骨细胞功能障碍和骨质流失的机制提供了新的见解。

原始出处:

Wei-Shiung Lian, Jih-Yang Ko, et al., Chaperonin 60 sustains osteoblast autophagy and counteracts glucocorticoid aggravation of osteoporosis by chaperoning RPTOR. Cell Death Dis. 2018 Oct; 9(10): 938.

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    2019-07-06 维他命
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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600357, encodeId=f066160035e55, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Wed Sep 26 06:06:00 CST 2018, time=2018-09-26, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1961146, encodeId=2c03196114669, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Jul 06 03:06:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870875, encodeId=855318e08752c, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600357, encodeId=f066160035e55, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Wed Sep 26 06:06:00 CST 2018, time=2018-09-26, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1961146, encodeId=2c03196114669, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Jul 06 03:06:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870875, encodeId=855318e08752c, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Wed Sep 26 06:06:00 CST 2018, time=2018-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1592497, encodeId=fe76159249e7b, content=<a href='/topic/show?id=6dc2101853ed' target=_blank style='color:#2F92EE;'>#骨质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=22, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101853, encryptionId=6dc2101853ed, topicName=骨质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e1d018108513, createdName=Eleven17, createdTime=Wed Sep 26 06:06:00 CST 2018, time=2018-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600357, encodeId=f066160035e55, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Wed Sep 26 06:06:00 CST 2018, time=2018-09-26, status=1, ipAttribution=)]
    2018-09-26 zhaojie88
  7. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600357, encodeId=f066160035e55, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Wed Sep 26 06:06:00 CST 2018, time=2018-09-26, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1961146, encodeId=2c03196114669, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sat Jul 06 03:06:00 CST 2019, time=2019-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870875, encodeId=855318e08752c, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600357, encodeId=f066160035e55, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Wed Sep 26 06:06:00 CST 2018, time=2018-09-26, status=1, ipAttribution=)]
    2018-09-26 cy0328
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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600357, encodeId=f066160035e55, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Wed Sep 26 06:06:00 CST 2018, time=2018-09-26, status=1, ipAttribution=)]
    2018-09-26 Eleven17
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