Arthritis Rheumatol:遗传因素导致小鼠创伤后骨关节炎变异的证据

2018-09-27 xiangting MedSci原创

PTOA的各种特征随遗传组成的不同而变化,这就证明了PTOA易感性的遗传基础。

由LG/J和SM/J杂交产生的重组同系繁殖(RI)小鼠品系为研究复杂遗传性状如骨关节炎(OA)提供了独特资源。研究人员确定了14个品种对创伤后OA(PTOA)各种表型特征的易感性。研究假设表型变异性与遗传变异性相关。

将10周龄雄性小鼠的内侧半月板去稳定化(DMM)以诱发PTOA。手术后8周处死小鼠并处理膝关节以进行组织学软骨变性和滑膜炎评分。使用Micro-CT分析骨小梁骨参数,其中包括软骨下骨板厚度和滑膜异位钙化。通过QuantiGene Plex测定评估膝关节中的基因表达。

广义遗传率范围为0.18-0.58,表明手术反应为中度可遗传。LGXSM-33、LGXSM-5、LGXSM-46和SM/J对OA高度易感,而LGXSM-131b、LGXSM-163、LGXSM-35、LGXSM-128a和LG/J对OA具有相对抗性。这项研究首次测量了PTOA特征性表型的遗传相关性:软骨退变与滑膜炎呈显著正相关(r=0.83-0.91),而软骨下骨板厚度与异位钙化呈负相关(r=-0.59)。此外,研究显示检测的78个基因中有40个与不同表型(OA)显著相关。与OA表型不同,没有证据表明DMM和SHAM膝关节中基因表达水平的差异存在遗传性变异。

对于这些小鼠品系,PTOA的各种特征随遗传组成的不同而变化,这就证明了PTOA易感性的遗传基础。建立了PTOA的遗传率。各种表型呈现出不同程度的相关性:(1)软骨退变与滑膜炎呈正相关,但(2)与异位钙化的形成无关。未来需要对OA基因所在的基因组区域和表达数据进行深入研究,以研究OA的机制和确定治疗靶标。

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    2019-06-15 lisa438
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    2018-09-29 lmm397
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  6. [GetPortalCommentsPageByObjectIdResponse(id=2026588, encodeId=947320265889d, content=<a href='/topic/show?id=e0b110159578' target=_blank style='color:#2F92EE;'>#骨关节#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101595, encryptionId=e0b110159578, topicName=骨关节)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=373b263, createdName=lisa438, createdTime=Sat Jun 15 04:21:00 CST 2019, time=2019-06-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1972540, encodeId=398b19e2540fd, content=<a href='/topic/show?id=8a6a2e8839' target=_blank style='color:#2F92EE;'>#Arthritis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2788, encryptionId=8a6a2e8839, topicName=Arthritis)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIibticIBly5jCSic5ZElW4He3rO4DMpUHUFaFX57OicNMnzckWaicBNeStwugWHFCuOdicoakApM4HGmtw/132, createdBy=f8672500006, createdName=ms6390871039024434, createdTime=Mon Mar 04 21:21:00 CST 2019, time=2019-03-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1265807, encodeId=5b94126580e72, content=<a href='/topic/show?id=57a53011364' target=_blank style='color:#2F92EE;'>#关节炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=30113, encryptionId=57a53011364, topicName=关节炎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f90281, createdName=lmm397, createdTime=Sat Sep 29 00:21:00 CST 2018, time=2018-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1335232, encodeId=6c451335232e5, content=<a href='/topic/show?id=e7cc32022c7' target=_blank style='color:#2F92EE;'>#创伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32022, encryptionId=e7cc32022c7, topicName=创伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=aa5a2500103, createdName=ms920641618706883, createdTime=Sat Sep 29 00:21:00 CST 2018, time=2018-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1342519, encodeId=4c2613425193a, content=<a href='/topic/show?id=34cb381023e' target=_blank style='color:#2F92EE;'>#变异#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38102, encryptionId=34cb381023e, topicName=变异)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=78c32500188, createdName=12498dabm77暂无昵称, createdTime=Sat Sep 29 00:21:00 CST 2018, time=2018-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1356937, encodeId=33e2135693ea7, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Sat Sep 29 00:21:00 CST 2018, time=2018-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1446350, encodeId=ce6b1446350e4, content=<a href='/topic/show?id=fa34950e8ce' target=_blank style='color:#2F92EE;'>#遗传因素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95078, encryptionId=fa34950e8ce, topicName=遗传因素)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJO58hUEwHTSriboUiaJJVJAFUh2Q9zFwDhIEx3o4vPWboomNEm7aRGHPjKslbcgez2BD57yUYH1FbQ/132, createdBy=16985204412, createdName=wjcjjian, createdTime=Sat Sep 29 00:21:00 CST 2018, time=2018-09-29, status=1, ipAttribution=)]
    2018-09-29 zhaojie88
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