Biomed Pharmacother:骨折患者如何预防cox-2特异性抑制剂的副作用

2019-08-08 不详 网络

已知COX-2特异性抑制剂可延缓骨折愈合并降低骨髓基质细胞的成骨潜能。然而,如何预防COX-2抑制剂的这些副作用尚不清楚。在本研究中,我们引入BMP9诱导的成骨分化作为模型,以评估全反式维甲酸(ATRA)是否可以通过改善COX-2特异性抑制剂对骨代谢的这些不利影响,并揭示可能的这个过程背后的机制。结果显示,ATRA增强了BMP9诱导成骨标志物的潜力,如碱性磷酸盐(ALP)和矿化结果所示;但视黄酸受

已知COX-2特异性抑制剂可延缓骨折愈合并降低骨髓基质细胞的成骨潜能。然而,如何预防COX-2抑制剂的这些副作用尚不清楚。在本研究中,我们引入BMP9诱导的成骨分化作为模型,以评估全反式维甲酸(ATRA)是否可以通过改善COX-2特异性抑制剂对骨代谢的这些不利影响,并揭示可能的这个过程背后的机制。

结果显示,ATRA增强了BMP9诱导成骨标志物的潜力,如碱性磷酸盐(ALP)和矿化结果所示;但视黄酸受体α(RARa)抑制剂显示出逆转作用。COX-2特异性抑制剂(NS398)降低了BMP9诱导的成骨标志物,而ATRA几乎消除了NS398的抑制作用。BMP9上调β-连环蛋白的蛋白质水平并促进其易位至细胞核,并且两者均被NS398降低。相反,ATRA显著减弱了NS398对BMP9增加的β-连环蛋白的抑制作用。外源性RXRa明显改善了沉默COX-2对BMP9诱导的异位骨形成的抑制作用。NS398降低了磷酸化CREB的水平,这几乎被ATRA逆转。此外,RXRa直接与磷酸化CREB相互作用,两者都在β-连环蛋白启动子区域募集。

综上所述,该研究结果表明,ATRA可以通过部分地增加Wnt/β-连环蛋白通路的活化来逆转COX-2抑制剂对骨代谢的副作用。

原始出处:

Wang H, Hu Y, et al., All-trans retinoic acid and COX-2 cross-talk to regulate BMP9-induced osteogenic differentiation via Wnt/β-catenin in mesenchymal stem cells. Biomed Pharmacother. 2019 Jul 31;118:109279. doi: 10.1016/j.biopha.2019.109279.

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    2020-04-04 jj000001
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    2019-10-09 sunylz
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    2020-01-09 yb6560
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  5. 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  6. [GetPortalCommentsPageByObjectIdResponse(id=1787628, encodeId=461e1e8762876, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Sat Apr 04 15:32:00 CST 2020, time=2020-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918814, encodeId=00bc1918814ad, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, 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  7. 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authenticateStatus=null, createdAvatar=null, createdBy=544412475251, createdName=手留余香, createdTime=Sat Aug 10 12:32:00 CST 2019, time=2019-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1609926, encodeId=b7481609926da, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sat Aug 10 12:32:00 CST 2019, time=2019-08-10, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1787628, encodeId=461e1e8762876, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=16, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Sat Apr 04 15:32:00 CST 2020, time=2020-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918814, encodeId=00bc1918814ad, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Wed Oct 09 21:32:00 CST 2019, time=2019-10-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996310, encodeId=f6bb199631099, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Thu Jan 09 18:32:00 CST 2020, time=2020-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798045, encodeId=0b951e98045fb, content=<a href='/topic/show?id=c1ba6e95292' target=_blank style='color:#2F92EE;'>#特异性抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=67952, 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encodeId=2f1b18243266c, content=<a href='/topic/show?id=56a932e7800' target=_blank style='color:#2F92EE;'>#副作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32778, encryptionId=56a932e7800, topicName=副作用)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8f0715, createdName=showtest, createdTime=Sun May 10 19:32:00 CST 2020, time=2020-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908559, encodeId=98331908559f2, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Wed Aug 21 07:32:00 CST 2019, time=2019-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1852079, encodeId=a46a18520e948, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Tue Oct 15 21:32:00 CST 2019, time=2019-10-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533678, encodeId=fbea15336e842, content=<a href='/topic/show?id=34e6514391' target=_blank style='color:#2F92EE;'>#COX-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5143, encryptionId=34e6514391, topicName=COX-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=544412475251, createdName=手留余香, createdTime=Sat Aug 10 12:32:00 CST 2019, time=2019-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1609926, encodeId=b7481609926da, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sat Aug 10 12:32:00 CST 2019, time=2019-08-10, status=1, ipAttribution=)]
    2019-10-15 jklm09
  9. 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  10. 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