Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifical...Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifically up-regulated in Schwann cells.Furthermore,using Schwann cell-specific Runx2 knocko ut mice,we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent.Changes observed in Runx2 knoc kout mice include increased prolife ration of Schwann cells,impaired Schwann cell migration and axonal regrowth,reduced re-myelination of axo ns,and a block in macrophage clearance in the late stage of regeneration.Taken together,our findings indicate that Runx2 is a key regulator of Schwann cell plasticity,and therefore peripheral nerve repair.Thus,our study shows that Runx2 plays a major role in Schwann cell migration,re-myelination,and peripheral nerve functional recovery following injury.展开更多
目的:探讨肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)对人脱落乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth,SHED)骨分化能力的影响,分析ERK1/2-Runx2信号通路在该调控过程中的变化。方法:从6~8岁健康儿童...目的:探讨肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)对人脱落乳牙牙髓干细胞(stem cells from human exfoliated deciduous teeth,SHED)骨分化能力的影响,分析ERK1/2-Runx2信号通路在该调控过程中的变化。方法:从6~8岁健康儿童正常乳恒牙替换即将脱落的乳切牙中分离和培养SHED,取第三代细胞,分为对照组(成骨诱导剂培养)、观察组(成骨诱导剂和TNF-α共培养)和激动剂组(成骨诱导剂、TNF-α和ERK通路激动剂共培养)。采用茜素红染色评价成骨分化功能,采用Western印迹检测SHED细胞中Osterix、OPN、ERK1/2、pERK1/2和Runx2的蛋白表达水平,应用qRT-PCR检测Osterix、OPN、ERK1/2、pERK1/2和Runx2 mRNA的表达。采用SPSS 26.0软件包对数据进行统计学分析。结果:3组细胞成骨分化能力比较结果显示,3组细胞中均可见红棕色矿化结节。3组组间相比,对照组矿化结节最多,激动剂组次之,观察组最少。与对照组相比,观察组和激动剂组的Osterix、OPN蛋白和mRNA表达水平显著下降,而激动剂组Osterix、OPN蛋白和mRNA表达水平显著高于观察组;3组细胞的ERK1/2蛋白和mRNA表达水平无显著差异,而观察组和激动剂组pERK1/2和Runx2的蛋白和mRNA表达水平显著高于对照组,激动剂组的蛋白及mRNA表达水平显著高于观察组。结论:TNF-α对SHED成骨分化具有抑制作用,该作用可能与抑制ERK1/2-Runx2信号通路有关。展开更多
基金supported by the National Natural Science Foundation of China,No.82104795 (to RH)。
文摘Runx2 is a major regulator of osteoblast differentiation and function;however,the role of Runx2 in peripheral nerve repair is unclea r.Here,we analyzed Runx2expression following injury and found that it was specifically up-regulated in Schwann cells.Furthermore,using Schwann cell-specific Runx2 knocko ut mice,we studied peripheral nerve development and regeneration and found that multiple steps in the regeneration process following sciatic nerve injury were Runx2-dependent.Changes observed in Runx2 knoc kout mice include increased prolife ration of Schwann cells,impaired Schwann cell migration and axonal regrowth,reduced re-myelination of axo ns,and a block in macrophage clearance in the late stage of regeneration.Taken together,our findings indicate that Runx2 is a key regulator of Schwann cell plasticity,and therefore peripheral nerve repair.Thus,our study shows that Runx2 plays a major role in Schwann cell migration,re-myelination,and peripheral nerve functional recovery following injury.
文摘目的 观察全杜仲胶囊对犬股骨头骨组织中的变化及对转录因子(RUNX2)、1型胶原蛋白(COL-1)蛋白表达的影响,探讨其修复股骨头坏死的机制。方法 选取健康成年比格犬(雌雄各6只,共12只,分笼饲养),随机数字表法分为正常组、模型组、全杜仲胶囊组、仙灵骨葆胶囊组,每组3只。除正常组外,其余3组均采用液氮冷冻法制备双侧股骨头坏死模型。术后第2天开始药物干预,正常组等量生理盐水灌胃,连续12周。观察犬的一般情况,苏木精-伊红染色法(HE)观察犬股骨头组织形态学改变;实时逆转录PCR(Real time RT-PCR)检测RUNX2、COL-1mRNA表达;免疫组化法检测RUNX2、COL-1蛋白表达。结果 与模型组相比较,HE病理染色方面,全杜仲组及仙灵骨葆胶囊组骨小梁面积、骨小梁体积有所恢复;免疫组化方面,与模型组相比,全杜仲胶囊组、仙灵骨葆胶囊组RUNX2蛋白和COL-1蛋白表达上升(P<0.05);Real time RT-PCR检测结果显示RUNX2、COL-1mRNA表达上升(P<0.05)。结论 全杜仲胶囊可以改善犬股骨头坏死组织的变化,这可能是通过调节COL-1及RUNX2蛋白及mRNA的表达调节骨代谢,进而达到防治股骨头坏死的目的。
