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Epigenetics:组蛋白去甲基化酶KDM4B可抑制破骨细胞的生成

2018-06-23 MedSci MedSci原创

牙周病(PD)困扰46%的美国人,目前没有有效的辅助疗法。尽管PD的大多数药物治疗靶,但宿主免疫应答是导致组织损伤和骨质丧失的主要原因。本研究中,我们确定组蛋白去甲基化酶KDM4B是用于治疗PD的潜在药物靶标。免疫组织化学染色显示患病牙周上皮KDM4B丰度增加,与炎症相关。在暴露于伴放线聚集杆菌脂多糖(Aa-LPS)的小鼠颅骨切片中,免疫组织化学染色显示KDM4B蛋白表达明显增加。已知8-羟基喹啉

牙周病(PD)困扰46%的美国人,目前没有有效的辅助疗法。尽管PD的大多数药物治疗靶,但宿主免疫应答是导致组织损伤和骨质丧失的主要原因。本研究中,我们确定组蛋白去甲基化酶KDM4B是用于治疗PD的潜在药物靶标。

免疫组织化学染色显示患病牙周上皮KDM4B丰度增加,与炎症相关。在暴露于伴放线聚集杆菌脂多糖(Aa-LPS)的小鼠颅骨切片中,免疫组织化学染色显示KDM4B蛋白表达明显增加。已知8-羟基喹啉ML324在体外抑制相关脱甲基酶KDM4E,但尚未针对任何其他靶标进行评估。该研究表明,ML324还可抑制KDM4B(IC50:4.9μM),并降低体外对Aa-LPS攻击的促炎细胞因子的应答。

研究结果还表明KDM4B间接抑制诱导的免疫抑制作用,需要新的蛋白质合成。此外,荧光染色的巨噬细胞表现出Aa-LPS攻击后甲基组蛋白3赖氨酸4(H3K4me)水平的显著降低,这是通过KDM4B抑制阻止的,表明这种作用是通过KDM1A介导的H3K4去甲基化产生。最后,破骨细胞祖细胞中KDM4B的ML324抑制显著降低了Aa-LPS诱导的破骨细胞生成。

综上所述,该研究结果将组蛋白甲基化与宿主对PD中细菌病原体的免疫应答联系起来,并提出了先前未报道的宿主炎性环境的表观遗传控制的可选机制。因此,KDM4B代表了治疗导致骨骼破坏的高度炎症性疾病的新的治疗靶点。

原始出处:


Kirkpatrick JE, Kirkwood KL, Woster PM. Inhibition of the Histone Demethylase KDM4B Leads to Activation of KDM1A, Attenuates Bacterial-Induced Pro-Inflammatory Cytokine Release, and Reduces Osteoclastogenesis. Epigenetics. 2018 Jun 21. doi: 10.1080/15592294.2018.1481703.

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    2019-01-13 canlab
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content=<a href='/topic/show?id=4cb5104495d' target=_blank style='color:#2F92EE;'>#KDM4B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10449, encryptionId=4cb5104495d, topicName=KDM4B)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3138208, createdName=zhanfl, createdTime=Fri Jan 18 10:03:00 CST 2019, time=2019-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1735747, encodeId=f0c01e357474b, content=<a href='/topic/show?id=9c363e259ba' target=_blank style='color:#2F92EE;'>#去甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37259, encryptionId=9c363e259ba, topicName=去甲基化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=031d33977719, createdName=AspirantSuo, createdTime=Fri May 24 06:03:00 CST 2019, time=2019-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1309984, encodeId=b5121309984a1, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jun 25 07:03:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
    2018-10-25 hunizi005
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time=2019-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1309984, encodeId=b5121309984a1, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jun 25 07:03:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
  5. 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  6. [GetPortalCommentsPageByObjectIdResponse(id=1686223, encodeId=f30f1686223da, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri Feb 22 00:03:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734020, encodeId=f3481e340206e, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, 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content=<a href='/topic/show?id=4cb5104495d' target=_blank style='color:#2F92EE;'>#KDM4B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10449, encryptionId=4cb5104495d, topicName=KDM4B)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3138208, createdName=zhanfl, createdTime=Fri Jan 18 10:03:00 CST 2019, time=2019-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1735747, encodeId=f0c01e357474b, content=<a href='/topic/show?id=9c363e259ba' target=_blank style='color:#2F92EE;'>#去甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37259, encryptionId=9c363e259ba, topicName=去甲基化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=031d33977719, createdName=AspirantSuo, createdTime=Fri May 24 06:03:00 CST 2019, time=2019-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1309984, encodeId=b5121309984a1, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jun 25 07:03:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
    2019-05-01 cy0324
  7. 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time=2019-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1309984, encodeId=b5121309984a1, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jun 25 07:03:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
    2018-11-11 huperzia
  8. [GetPortalCommentsPageByObjectIdResponse(id=1686223, encodeId=f30f1686223da, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri Feb 22 00:03:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734020, encodeId=f3481e340206e, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, createdName=canlab, createdTime=Sun Jan 13 10:03:00 CST 2019, time=2019-01-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2028082, encodeId=2e84202808222, content=<a href='/topic/show?id=cc2010448e6' target=_blank style='color:#2F92EE;'>#KDM4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10448, encryptionId=cc2010448e6, topicName=KDM4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=49ef408, createdName=hunizi005, createdTime=Thu Oct 25 06:03:00 CST 2018, time=2018-10-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798664, encodeId=4c9f1e986640a, content=<a href='/topic/show?id=169069e8530' target=_blank style='color:#2F92EE;'>#甲基化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69785, encryptionId=169069e8530, topicName=甲基化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=af60254, createdName=mhm289, createdTime=Thu Aug 02 00:03:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1785740, encodeId=d1921e8574063, content=<a href='/topic/show?id=9e1a688138' target=_blank style='color:#2F92EE;'>#epigenetics#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6881, encryptionId=9e1a688138, topicName=epigenetics)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=96f62500201, createdName=12498e67m28暂无昵称, createdTime=Thu Mar 14 14:03:00 CST 2019, time=2019-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2049048, encodeId=85412049048fc, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Wed May 01 04:03:00 CST 2019, time=2019-05-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1877993, encodeId=da0118e799369, content=<a href='/topic/show?id=5d80e943ef' target=_blank style='color:#2F92EE;'>#Genetics#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7943, encryptionId=5d80e943ef, topicName=Genetics)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca89104, createdName=huperzia, createdTime=Sun Nov 11 03:03:00 CST 2018, time=2018-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1968649, encodeId=65c519686490b, content=<a href='/topic/show?id=4cb5104495d' target=_blank style='color:#2F92EE;'>#KDM4B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10449, encryptionId=4cb5104495d, topicName=KDM4B)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3138208, createdName=zhanfl, createdTime=Fri Jan 18 10:03:00 CST 2019, time=2019-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1735747, encodeId=f0c01e357474b, content=<a href='/topic/show?id=9c363e259ba' target=_blank style='color:#2F92EE;'>#去甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37259, encryptionId=9c363e259ba, topicName=去甲基化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=031d33977719, createdName=AspirantSuo, createdTime=Fri May 24 06:03:00 CST 2019, time=2019-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1309984, encodeId=b5121309984a1, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jun 25 07:03:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
    2019-01-18 zhanfl
  9. [GetPortalCommentsPageByObjectIdResponse(id=1686223, encodeId=f30f1686223da, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri Feb 22 00:03:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734020, encodeId=f3481e340206e, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, 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objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Wed May 01 04:03:00 CST 2019, time=2019-05-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1877993, encodeId=da0118e799369, content=<a href='/topic/show?id=5d80e943ef' target=_blank style='color:#2F92EE;'>#Genetics#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7943, encryptionId=5d80e943ef, topicName=Genetics)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca89104, createdName=huperzia, createdTime=Sun Nov 11 03:03:00 CST 2018, time=2018-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1968649, encodeId=65c519686490b, content=<a href='/topic/show?id=4cb5104495d' target=_blank style='color:#2F92EE;'>#KDM4B#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10449, encryptionId=4cb5104495d, topicName=KDM4B)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3138208, createdName=zhanfl, createdTime=Fri Jan 18 10:03:00 CST 2019, time=2019-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1735747, encodeId=f0c01e357474b, content=<a href='/topic/show?id=9c363e259ba' target=_blank style='color:#2F92EE;'>#去甲基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37259, encryptionId=9c363e259ba, topicName=去甲基化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=031d33977719, createdName=AspirantSuo, createdTime=Fri May 24 06:03:00 CST 2019, time=2019-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1309984, encodeId=b5121309984a1, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jun 25 07:03:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
  10. [GetPortalCommentsPageByObjectIdResponse(id=1686223, encodeId=f30f1686223da, content=<a href='/topic/show?id=66f3e93862' target=_blank style='color:#2F92EE;'>#Genet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7938, encryptionId=66f3e93862, topicName=Genet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=爆笑小医, createdTime=Fri Feb 22 00:03:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734020, encodeId=f3481e340206e, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, 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time=2019-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1309984, encodeId=b5121309984a1, content=<a href='/topic/show?id=2830e349460' target=_blank style='color:#2F92EE;'>#破骨细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73494, encryptionId=2830e349460, topicName=破骨细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Mon Jun 25 07:03:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
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