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Stem Cells Int:间充质干细胞通过抑制TNF-α促进胶原诱导的关节炎小鼠的成骨作用

2018-06-23 MedSci MedSci原创

本研究旨在探讨脐带间充质干细胞(UC-MSC)移植对胶原诱导性关节炎(CIA)小鼠关节损伤和骨质疏松症的影响,并探讨UC-MSCs调节成骨分化的机制。 将CIA小鼠分为以下处理组:UC-MSC移植组,抗肿瘤坏死因子(TNF-α)组和唑来膦酸(ZA)组。使用微型计算机断层扫描(micro-CT)分析骨形态学参数。测定处理的CIA小鼠的成骨分化。在体外使用TNF-α处理来自CIA小鼠的骨髓间充质干细胞

本研究旨在探讨脐带间充质干细胞(UC-MSC)移植对胶原诱导性关节炎(CIA)小鼠关节损伤和骨质疏松症的影响,并探讨UC-MSCs调节成骨分化的机制。

将CIA小鼠分为以下处理组:UC-MSC移植组,抗肿瘤坏死因子(TNF-α)组和唑来膦酸(ZA)组。使用微型计算机断层扫描(micro-CT)分析骨形态学参数。测定处理的CIA小鼠的成骨分化。在体外使用TNF-α处理来自CIA小鼠的骨髓间充质干细胞(BM-MSC)以探索其对骨生成的作用。

结果显示,与对照小鼠相比,在UC-MSC移植和抗TNF-α处理的CIA组中关节炎评分明显降低(P <0.001)。Micro-CT显示,CIA小鼠在免疫后12周发生骨质疏松症。在UC-MSC处理的CIA小鼠中骨形态学参数部分改善。与DBA/1小鼠相比,CIA小鼠成骨分化功能受损,表现为ALP活性降低(P <0.001),成骨标记基因的mRNA和蛋白质水平降低(P <0.05)。UC-MSC治疗显著加重CIA小鼠中成骨分化能力受损。同时,UC-MSC组血清TNF-α的水平明显下降。在体外加入TNF-α后,成骨作用减弱。

综上所述,这项研究表明,UC-MSC移植不仅明显改善了关节损伤,而且在CIA小鼠的骨质疏松症中发挥了有益作用。从机制上看,通过抑制TNF-α可以在UC-MSC治疗下改善CIA的成骨分化。

原始出处:


Liu C, Zhang H, et al., Mesenchymal Stem Cells Promote the Osteogenesis in Collagen-Induced Arthritic Mice through the Inhibition of TNF-α. Stem Cells Int. 2018 May 8;2018:4069032. doi: 10.1155/2018/4069032. eCollection 2018.

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    2018-07-17 维他命
  4. 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content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Mon Jun 25 12:39:00 CST 2018, time=2018-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482151, encodeId=4b9d1482151c1, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, 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  5. 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createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Wed Nov 14 07:39:00 CST 2018, time=2018-11-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1960979, encodeId=f25819609e9b2, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, 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=Tue Jul 17 16:39:00 CST 2018, time=2018-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870710, encodeId=336418e071083, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, 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content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Mon Jun 25 12:39:00 CST 2018, time=2018-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482151, encodeId=4b9d1482151c1, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, 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  6. [GetPortalCommentsPageByObjectIdResponse(id=1815337, encodeId=4f0a181533efb, content=<a href='/topic/show?id=ae359e231d4' target=_blank style='color:#2F92EE;'>#间充质干细#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97231, encryptionId=ae359e231d4, topicName=间充质干细)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b632500090, createdName=h.y200607_23674418, createdTime=Mon Apr 22 01:39:00 CST 2019, time=2019-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1794608, encodeId=77e21e9460807, content=<a href='/topic/show?id=82b416e79f5' target=_blank style='color:#2F92EE;'>#stem cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16779, encryptionId=82b416e79f5, topicName=stem cell)], attachment=null, authenticateStatus=null, 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content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Mon Jun 25 12:39:00 CST 2018, time=2018-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482151, encodeId=4b9d1482151c1, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Mon Jun 25 12:39:00 CST 2018, time=2018-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615007, encodeId=00ca161500ece, content=<a href='/topic/show?id=d74a44e2e7' target=_blank style='color:#2F92EE;'>#cells#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4472, encryptionId=d74a44e2e7, topicName=cells)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=659819575782, createdName=124988c7m101暂无昵称, createdTime=Mon Jun 25 12:39:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
    2018-06-25 lmm397
  7. 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authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Mon Jun 25 12:39:00 CST 2018, time=2018-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1615007, encodeId=00ca161500ece, content=<a href='/topic/show?id=d74a44e2e7' target=_blank style='color:#2F92EE;'>#cells#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4472, encryptionId=d74a44e2e7, topicName=cells)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=659819575782, createdName=124988c7m101暂无昵称, createdTime=Mon Jun 25 12:39:00 CST 2018, time=2018-06-25, status=1, ipAttribution=)]
    2018-06-25 zhaojie88
  8. 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    2018-06-25 snowpeakxu
  9. 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  10. 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Sci Rep:CPT1C通过调节自噬促进葡萄糖剥夺下的人类间充质干细胞的存活

人类间充质干细胞(hMSCs)广泛用于再生医学。在一些应用中,hMSCs必须在由血管生成引起的低营养条件下存活。改善hMSCs的存活或与组织工程具有高度相关性。肉碱棕榈酰转移酶1C(CPT1C)是在神经元和癌细胞中专一表达的假酶。在本研究中,研究人员发现CPT1C也在hMSCs中表达,并保护它们抵抗葡萄糖饥饿、糖酵解抑制和氧/葡萄糖剥夺。 结果显示,hMSCs中CPT1C过表达不增加脂肪酸氧

Bull Exp Biol Med:内皮细胞调节间充质干细胞的分化潜能和迁移能力

本研究中,我们研究了内皮细胞对多潜能间充质基质细胞体外迁移和分化潜能的影响。结果显示,在存在完整的和TNFα激活的内皮细胞的情况下,干细胞基因OCT4,SOX2和成软骨分化调节剂SOX9基因下调,成骨主基因RUNX2在间充质基质细胞中上调,这表明间充质基质细胞承担能力增加。由内皮细胞调节的培养基刺激间充质基质细胞的迁移活性,与来自非活化细胞的培养基相比,来自活化细胞的条件培养基中的细胞迁移率明显增

Sci Rep:研究揭示Wnt11在人骨髓间充质干细胞向微结构化钛表面成骨分化中的作用

骨内植入物的成功骨整合涉及种植体表面间充质干细胞(MSC)的迁移和分化。在缺乏培养基添加剂的聚苯乙烯(TCPS)孔板中的培养基中,亲水性钛表面可诱导MSCs在体外进行成骨细胞分化。这个过程涉及非经典的Wnt5a,与经典的Wnt3a相比,Wnt5a在TCPS上通常具有成骨细胞分化能力。Wnt蛋白参与形态发育和组织形成,表明其他的Wnt可能参与了此过程。本研究中,研究人员证明Wnt11是MSCs成骨分

Stem Cells Int:聚丁二酸丁二醇酯3D支架促进人类间充质干细胞生长和成骨作用

聚丁二酸丁二醇酯(PBS)是一种可生物降解的聚酯,与聚乳酸(PLA)相比,具有更好的可加工性和多种机械性能。目前仅有少数研究评估了含有PBS的骨TE材料,我们制备了PLA-PBS混合材料并分析了材料特性以及人骨髓间充质干细胞(hMSCs)在支架上的细胞附着、增殖和成骨分化。除PLA、PBS和PLA-PBS混合物外,还评价了PLA-聚己内酯和PLA-聚(三亚甲基碳酸酯)混合物。使用熔体纺丝制备聚合物

Biopolymers:BMP-7衍生的肽修饰的藻酸盐多孔支架促进人间充质干细胞的聚集和骨分化

基于干细胞的骨组织工程的支架应具备指导干细胞骨分化的能力。否则,干细胞将分化成不需要的细胞类型或将在体内形成肿瘤。藻酸盐是一种具有良好生物相容性的天然多糖,广泛应用于生物医学领域。然而,原始藻酸盐较差的生物活性和成骨能力阻碍了其在组织工程中的进一步应用。 在这项工作中,来源于骨形态发生蛋白-7的骨形成肽-1(BFP-1)移植到海藻酸聚合物链上以制备肽修饰的藻酸盐多孔支架(pep-APS)以促

Stem Cells Int:罗米地辛通过抑制组蛋白脱乙酰酶活性促进人类间充质干细胞的成骨和成脂分化

骨髓间充质干细胞(BMSCs)是一种多潜能干细胞,可分化成中胚层谱系细胞,包括脂肪细胞和成骨细胞。然而,关于控制骨髓间充质干细胞向脂肪细胞或成骨细胞的谱系特异性分化的表观遗传机制目前尚未清楚。本研究中,研究人员通过表观功能筛选库确定了一种靶向HDAC1和HDAC2小分子双重抑制剂——罗米地辛的表观学效应。 结果显示,暴露于罗米地辛(5nM)的BMSCs表现出更强的脂肪细胞和成骨细胞分化。差异

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