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Biochim Biophys Acta:研究揭示PEDF调节基质矿化的机制

2018-09-03 MedSci MedSci原创

编码色素上皮衍生因子(PEDF)的Serpinf1基因的突变导致VI型成骨不全,其标志是矿化缺陷。我们报道PEDF抑制Sost/Sclerostin和其他骨细胞相关基因在矿化成骨细胞培养物中的表达,并表明这可能是PEDF调节基质矿化的机制的一部分。 我们使用长期分化的矿化成骨细胞培养物(LTD)来确定PEDF调节骨细胞基因表达的机制。在成骨培养基中培养人成骨细胞4个月,然后分析骨细胞相关基因

编码色素上皮衍生因子(PEDF)的Serpinf1基因的突变导致VI型成骨不全,其标志是矿化缺陷。我们报道PEDF抑制Sost/Sclerostin和其他骨细胞相关基因在矿化成骨细胞培养物中的表达,并表明这可能是PEDF调节基质矿化的机制的一部分。

我们使用长期分化的矿化成骨细胞培养物(LTD)来确定PEDF调节骨细胞基因表达的机制。在成骨培养基中培养人成骨细胞4个月,然后分析骨细胞相关基因和编码蛋白来建立LTD培养物。LTD细胞合成了硬化蛋白、基质细胞外磷酸糖蛋白(MEPE)和牙本质基质蛋白(DMP-1),并通过PEDF处理降低了其合成。

使用PEDF处理培养物诱导Erk和糖原合成酶激酶3-β(GSK-3β)的磷酸化,以及非磷酸化β-连环蛋白的积累。在PEDF存在下,抑制Erk活化和针对色素上皮衍生受体(PEDF-R)的中和抗体抑制GSK-3β磷酸化和非磷酸化β-连环蛋白的积累。Topflash测定证明PEDF激活荧光素酶报告基因活性,并且通过用Erk抑制剂或针对PEDF-R的中和抗体处理来抑制该活性。在PEDF存在下Dickkopf相关蛋白1处理细胞的作用最小,表明GSK-3β磷酸化和非磷酸化β-连环蛋白的积累可能不涉及骨细胞中的LRP5/6。

总之,该研究结果表明PEDF通过其受体调节骨细胞基因表达,并且可能涉及Erk/GSK-3β/β-连环蛋白信号传导通路。

原始出处:

Li F, Cain JD, et al., Pigment epithelium derived factor regulates human Sost/Sclerostin and other osteocyte gene expression via the receptor and induction of Erk/GSK-3beta/beta-catenin signaling. Biochim Biophys Acta. 2018 Aug 1. pii: S0925-4439(18)30283-7. doi: 10.1016/j.bbadis.2018.07.034.

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    2019-07-03 feather89
  3. 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    2019-05-22 yahu
  4. 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objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/C20CB8E4EBB36F5B821651C710BCB491/100, createdBy=18de1715848, createdName=lofter, createdTime=Tue Sep 04 06:53:19 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342385, encodeId=f92f34238509, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfBfgWn9nXBgH1sNSiaOAKhsKpN40jDHQKqcRzovau5VibLvREN8uxnu9sKoScBicHSiaDMmbveibFdrBiaD4k4IOPwlG/0, createdBy=b5d11730951, createdName=Jackie Li, createdTime=Mon Sep 03 07:16:12 CST 2018, time=2018-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342372, encodeId=7af63423e2cb, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Mon Sep 03 06:37:33 CST 2018, time=2018-09-03, status=1, ipAttribution=)]
    2019-08-15 windight
  5. 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content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Mon Sep 03 06:37:33 CST 2018, time=2018-09-03, status=1, ipAttribution=)]
    2019-02-28 sunylz
  6. 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  7. 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content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Mon Sep 03 06:37:33 CST 2018, time=2018-09-03, status=1, ipAttribution=)]
    2018-09-04 liumin1987

    嗯嗯,学习了。

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1757116, encodeId=11a11e57116f2, content=<a href='/topic/show?id=103b421e0e8' target=_blank style='color:#2F92EE;'>#基质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42170, encryptionId=103b421e0e8, topicName=基质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=281337296540, createdName=ms7899726347904398, createdTime=Wed Mar 13 01:10:00 CST 2019, time=2019-03-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1727571, encodeId=e7911e27571ca, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f06c33759375, createdName=feather89, createdTime=Wed Jul 03 15:10:00 CST 2019, time=2019-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1721312, encodeId=cb7f1e213124d, content=<a href='/topic/show?id=0143e3298c3' target=_blank style='color:#2F92EE;'>#矿化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73298, encryptionId=0143e3298c3, topicName=矿化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2a5532986439, createdName=yahu, createdTime=Wed May 22 02:10:00 CST 2019, time=2019-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1849615, encodeId=dfab1849615ab, content=<a href='/topic/show?id=61815385aa' target=_blank style='color:#2F92EE;'>#CTA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5385, encryptionId=61815385aa, topicName=CTA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Thu Aug 15 02:10:00 CST 2019, time=2019-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918271, encodeId=cc4a19182e17e, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Thu Feb 28 01:10:00 CST 2019, time=2019-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1707556, encodeId=99a31e07556fb, content=<a href='/topic/show?id=9f7c99e256' target=_blank style='color:#2F92EE;'>#IOP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9972, encryptionId=9f7c99e256, topicName=IOP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bb031431834, createdName=124987c6m46暂无昵称, createdTime=Thu Dec 27 05:10:00 CST 2018, time=2018-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342632, encodeId=c72034263221, content=嗯嗯,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/07/16/3b24606172648eea459125cb74754afe.jpg, createdBy=6c022216608, createdName=liumin1987, createdTime=Tue Sep 04 10:21:27 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342579, encodeId=13b43425e955, content=学习了感谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/C20CB8E4EBB36F5B821651C710BCB491/100, createdBy=18de1715848, createdName=lofter, createdTime=Tue Sep 04 06:53:19 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342385, encodeId=f92f34238509, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfBfgWn9nXBgH1sNSiaOAKhsKpN40jDHQKqcRzovau5VibLvREN8uxnu9sKoScBicHSiaDMmbveibFdrBiaD4k4IOPwlG/0, createdBy=b5d11730951, createdName=Jackie Li, createdTime=Mon Sep 03 07:16:12 CST 2018, time=2018-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342372, encodeId=7af63423e2cb, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Mon Sep 03 06:37:33 CST 2018, time=2018-09-03, status=1, ipAttribution=)]
    2018-09-04 lofter

    学习了感谢分享

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1757116, encodeId=11a11e57116f2, content=<a href='/topic/show?id=103b421e0e8' target=_blank style='color:#2F92EE;'>#基质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42170, encryptionId=103b421e0e8, topicName=基质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=281337296540, createdName=ms7899726347904398, createdTime=Wed Mar 13 01:10:00 CST 2019, time=2019-03-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1727571, encodeId=e7911e27571ca, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f06c33759375, createdName=feather89, createdTime=Wed Jul 03 15:10:00 CST 2019, time=2019-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1721312, encodeId=cb7f1e213124d, content=<a href='/topic/show?id=0143e3298c3' target=_blank style='color:#2F92EE;'>#矿化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73298, encryptionId=0143e3298c3, topicName=矿化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2a5532986439, createdName=yahu, createdTime=Wed May 22 02:10:00 CST 2019, time=2019-05-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1849615, encodeId=dfab1849615ab, content=<a href='/topic/show?id=61815385aa' target=_blank style='color:#2F92EE;'>#CTA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5385, encryptionId=61815385aa, topicName=CTA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Thu Aug 15 02:10:00 CST 2019, time=2019-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918271, encodeId=cc4a19182e17e, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Thu Feb 28 01:10:00 CST 2019, time=2019-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1707556, encodeId=99a31e07556fb, content=<a href='/topic/show?id=9f7c99e256' target=_blank style='color:#2F92EE;'>#IOP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9972, encryptionId=9f7c99e256, topicName=IOP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bb031431834, createdName=124987c6m46暂无昵称, createdTime=Thu Dec 27 05:10:00 CST 2018, time=2018-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342632, encodeId=c72034263221, content=嗯嗯,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/07/16/3b24606172648eea459125cb74754afe.jpg, createdBy=6c022216608, createdName=liumin1987, createdTime=Tue Sep 04 10:21:27 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342579, encodeId=13b43425e955, content=学习了感谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/C20CB8E4EBB36F5B821651C710BCB491/100, createdBy=18de1715848, createdName=lofter, createdTime=Tue Sep 04 06:53:19 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342385, encodeId=f92f34238509, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfBfgWn9nXBgH1sNSiaOAKhsKpN40jDHQKqcRzovau5VibLvREN8uxnu9sKoScBicHSiaDMmbveibFdrBiaD4k4IOPwlG/0, createdBy=b5d11730951, createdName=Jackie Li, createdTime=Mon Sep 03 07:16:12 CST 2018, time=2018-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342372, encodeId=7af63423e2cb, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Mon Sep 03 06:37:33 CST 2018, time=2018-09-03, status=1, ipAttribution=)]
    2018-09-03 Jackie Li

    学习

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=1757116, encodeId=11a11e57116f2, content=<a href='/topic/show?id=103b421e0e8' target=_blank style='color:#2F92EE;'>#基质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42170, encryptionId=103b421e0e8, topicName=基质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=281337296540, createdName=ms7899726347904398, createdTime=Wed Mar 13 01:10:00 CST 2019, time=2019-03-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1727571, encodeId=e7911e27571ca, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, 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topicList=[TopicDto(id=5385, encryptionId=61815385aa, topicName=CTA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ec9955, createdName=windight, createdTime=Thu Aug 15 02:10:00 CST 2019, time=2019-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1918271, encodeId=cc4a19182e17e, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Thu Feb 28 01:10:00 CST 2019, time=2019-02-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1707556, encodeId=99a31e07556fb, content=<a href='/topic/show?id=9f7c99e256' target=_blank style='color:#2F92EE;'>#IOP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9972, encryptionId=9f7c99e256, topicName=IOP)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bb031431834, createdName=124987c6m46暂无昵称, createdTime=Thu Dec 27 05:10:00 CST 2018, time=2018-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342632, encodeId=c72034263221, content=嗯嗯,学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2018/07/16/3b24606172648eea459125cb74754afe.jpg, createdBy=6c022216608, createdName=liumin1987, createdTime=Tue Sep 04 10:21:27 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342579, encodeId=13b43425e955, content=学习了感谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/C20CB8E4EBB36F5B821651C710BCB491/100, createdBy=18de1715848, createdName=lofter, createdTime=Tue Sep 04 06:53:19 CST 2018, time=2018-09-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342385, encodeId=f92f34238509, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfBfgWn9nXBgH1sNSiaOAKhsKpN40jDHQKqcRzovau5VibLvREN8uxnu9sKoScBicHSiaDMmbveibFdrBiaD4k4IOPwlG/0, createdBy=b5d11730951, createdName=Jackie Li, createdTime=Mon Sep 03 07:16:12 CST 2018, time=2018-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=342372, encodeId=7af63423e2cb, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Mon Sep 03 06:37:33 CST 2018, time=2018-09-03, status=1, ipAttribution=)]
    2018-09-03 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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