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Cell Metab:肝骨轴缺陷促进肝性骨营养不良疾病的发生机制

2022-04-03 MedSci原创 MedSci原创

南京大学医学院蒋青教授研究团队与南京医科大学附属逸夫医院薛斌教授团队、南京医科大学李朝军教授团队、中科院深圳先进技术研究院陈棣教授团队合作,在肝性骨病发生机制研究方面取得进展。研究成果以“

南京大学医学院蒋青教授研究团队与南京医科大学附属逸夫医院薛斌教授团队、南京医科大学李朝军教授团队、中科院深圳先进技术研究院陈棣教授团队合作,在肝性骨病发生机制研究方面取得进展。研究成果以“肝骨轴缺陷促进肝性骨营养不良疾病的进展(Defects in a liver-bone axis contribute to hepatic osteodystrophy disease progression)”为题,于2022年3月1日在线发表于《细胞代谢》(Cell Metabolism)。

肝性骨病(Hepatic Osteodystrophy)又称肝性骨营养不良,是一类慢性肝损伤患者中出现骨矿物质密度整体改变的代谢性骨骼疾病,多由病毒性肝炎、肝硬化、脂肪肝引发。全球慢性肝损伤患者已超过8.4亿,并以每年200万的速度增长。其中,约 12%~55%的患者可出现骨质疏松或骨量降低,同时这些患者的骨折风险高达5.3%。2016年中国非酒精性脂肪性肝炎(NASH)患者为3261万例,肝硬化患者为109万例,因肝脏功能紊乱影响骨代谢平衡而导致的骨质疏松和脆性骨折,严重影响患者生活质量和长期预后,给社会、医疗和患者均造成了巨大负担。因此,阐明肝性骨病发生发展的作用机制,具有重要的科学意义及临床应用前景。

该合作团队研究表明,经典内分泌器官肝脏与非经典内分泌器官骨骼之间存在着轴向的稳态调控,一旦稳态平衡被破坏,便会导致肝性骨病的发生。该研究在临床肝性骨病患者以及小鼠模型中发现,肝脏内磷酸酶PP2Acα表达量显著增加。肝脏内特异性敲除PP2Acα能够促进肝脏分泌卵磷脂胆固醇脂酰基转移酶(LCAT),通过胆固醇逆向转运来改变肝骨轴平衡,缓解小鼠骨量丢失,改善肝性骨病。LCAT一方面促进成骨细胞活性、抑制破骨细胞成熟,调节骨代谢并改善骨量;另一方面缓解肝损伤,从而发挥双向调节肝性骨病的作用(图)。

 

图 PP2Acα-LCAT调控肝性骨病的发生发展的作用机制

该研究不仅揭示了肝骨轴在肝性骨病进展中重要的调控机制,也提供了器官之间相互作用调控的理论基础,并为肝性骨病药物治疗提供了潜在作用靶点。

原始出处:

Lu K, Shi TS, Shen SY, Shi Y, Gao HL, Wu J, Lu X, Gao X, Ju HX, Wang W, Cao Y, Chen D, Li CJ, Xue B, Jiang Q.Defects in a liver-bone axis contribute to hepatic osteodystrophy disease progression.Cell Metab. 2022 Mar 1;34(3):441-457.e7. doi: 10.1016/j.cmet.2022.02.006

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    2023-03-12 一闲
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    2022-04-06 guojianrong
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    2023-03-16 维他命
  5. [GetPortalCommentsPageByObjectIdResponse(id=1872404, encodeId=5d6a18e24045f, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon May 09 22:51:22 CST 2022, time=2022-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896997, encodeId=3e4a189699e90, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Sun Mar 12 20:51:22 CST 2023, time=2023-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888424, encodeId=ec8e188842461, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Wed Apr 06 12:51:22 CST 2022, time=2022-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962730, encodeId=397a1962e30cb, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Thu Mar 16 01:51:22 CST 2023, time=2023-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511320, encodeId=bcc21511320f1, content=<a href='/topic/show?id=0a493e89802' target=_blank style='color:#2F92EE;'>#发生机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37898, encryptionId=0a493e89802, topicName=发生机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=188310331118, createdName=ms6390871039024434, createdTime=Tue Apr 05 13:51:22 CST 2022, time=2022-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1208491, encodeId=a62f120849114, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b9d2233692, createdName=1212ba38m22暂无昵称, createdTime=Mon Apr 04 09:33:38 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1208472, encodeId=b83412084e2d0, content=受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210809/ad098dd9e1974981975c3e5164b1e05d/8e3bab002ce344ddbcd7632c3d7a3a64.jpg, createdBy=2f582169660, createdName=玉兰儿, createdTime=Mon Apr 04 06:22:35 CST 2022, time=2022-04-04, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1872404, encodeId=5d6a18e24045f, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon May 09 22:51:22 CST 2022, time=2022-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896997, encodeId=3e4a189699e90, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Sun Mar 12 20:51:22 CST 2023, time=2023-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888424, encodeId=ec8e188842461, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Wed Apr 06 12:51:22 CST 2022, time=2022-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962730, encodeId=397a1962e30cb, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Thu Mar 16 01:51:22 CST 2023, time=2023-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511320, encodeId=bcc21511320f1, content=<a href='/topic/show?id=0a493e89802' target=_blank style='color:#2F92EE;'>#发生机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37898, encryptionId=0a493e89802, topicName=发生机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=188310331118, createdName=ms6390871039024434, createdTime=Tue Apr 05 13:51:22 CST 2022, time=2022-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1208491, encodeId=a62f120849114, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b9d2233692, createdName=1212ba38m22暂无昵称, createdTime=Mon Apr 04 09:33:38 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1208472, encodeId=b83412084e2d0, content=受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210809/ad098dd9e1974981975c3e5164b1e05d/8e3bab002ce344ddbcd7632c3d7a3a64.jpg, createdBy=2f582169660, createdName=玉兰儿, createdTime=Mon Apr 04 06:22:35 CST 2022, time=2022-04-04, status=1, ipAttribution=)]
    2022-04-04 1212ba38m22暂无昵称

    学习了

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1872404, encodeId=5d6a18e24045f, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon May 09 22:51:22 CST 2022, time=2022-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896997, encodeId=3e4a189699e90, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Sun Mar 12 20:51:22 CST 2023, time=2023-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888424, encodeId=ec8e188842461, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Wed Apr 06 12:51:22 CST 2022, time=2022-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1962730, encodeId=397a1962e30cb, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, 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=Thu Mar 16 01:51:22 CST 2023, time=2023-03-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1511320, encodeId=bcc21511320f1, content=<a href='/topic/show?id=0a493e89802' target=_blank style='color:#2F92EE;'>#发生机制#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37898, encryptionId=0a493e89802, topicName=发生机制)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=188310331118, createdName=ms6390871039024434, createdTime=Tue Apr 05 13:51:22 CST 2022, time=2022-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1208491, encodeId=a62f120849114, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b9d2233692, createdName=1212ba38m22暂无昵称, createdTime=Mon Apr 04 09:33:38 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1208472, encodeId=b83412084e2d0, content=受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210809/ad098dd9e1974981975c3e5164b1e05d/8e3bab002ce344ddbcd7632c3d7a3a64.jpg, createdBy=2f582169660, createdName=玉兰儿, createdTime=Mon Apr 04 06:22:35 CST 2022, time=2022-04-04, status=1, ipAttribution=)]
    2022-04-04 玉兰儿

    受益

    0

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