目的基于大鼠骨形态发生蛋白2(bone morphogenetic protein2,BMP2)/Smad家族成员1(smad family member 1,Smad1)通路,探究重组人转化生长因子-β1(recombinant human transforming growth factor-β1,rhTGF-β1)对正畸牙移动(orthodonti...目的基于大鼠骨形态发生蛋白2(bone morphogenetic protein2,BMP2)/Smad家族成员1(smad family member 1,Smad1)通路,探究重组人转化生长因子-β1(recombinant human transforming growth factor-β1,rhTGF-β1)对正畸牙移动(orthodontic tooth movement,OMT)大鼠破骨细胞形成的影响。方法构建大鼠OTM模型,采用显微CT(Micro-CT)分析测定OTM的距离;通过抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色评估压力侧破骨细胞活性;苏木精-伊红(hematoxylin and eosin,HE)染色评估压力侧组织形态学特征,免疫组化(immunohistochemistry,IHC)染色和蛋白质印迹(Western blot)测定相关蛋白表达水平。结果与正常组相比,Model组大鼠OTM距离增加(P<0.01),牙周间隙明显变窄并出现吸收陷窝,压力侧的基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)、核因子κB受体活化因子配体(receptor activator of nuclear factor kappa B ligand,RANKL)增加(P<0.01)、骨保护素(osteoprotegerin,OPG)表达降低(P<0.01),BMP2/Smad1信号通路被激活(P<0.01)。经BMP2抑制剂Noggin处理后,与Model组相比,BMP2、p-Smad1表达显著降低(P<0.01),OTM距离显著降低(P<0.01),且压力侧的TRAP、MMP-9及RANKL表达均显著降低(P<0.01),OPG升高(P<0.01)。经rhTGF-β1处理的大鼠中,较Model组OTM距离显著增加(P<0.01),TRAP阳性多核细胞数量升高(P<0.01),压力侧的MMP-9及RANKL表达均显著升高(P<0.05)、OPG表达显著降低(P<0.01),且BMP2、p-Smad1表达上调(P<0.01)。此外,rhTGF-β1+Noggin组部分逆转了rhTGF-β1组大鼠的破骨细胞数量的增加效应(P<0.01)。结论正畸力可促进破骨细胞形成,且rhTGF-β1可通过BMP2/Smad1信号通路增强OTM过程中破骨细胞的形成。展开更多
目的:探讨序贯激光结合^(32)P同位素敷贴协同治疗烧伤增生性瘢痕的疗效及对瘢痕组织TGF-β_(1)、BMP-7的影响。方法:选择2021年3月-2023年3月在笔者医院收治的124例烧伤增生性瘢痕患者,随机分为对照组和观察组,每组62例。对照组患者均...目的:探讨序贯激光结合^(32)P同位素敷贴协同治疗烧伤增生性瘢痕的疗效及对瘢痕组织TGF-β_(1)、BMP-7的影响。方法:选择2021年3月-2023年3月在笔者医院收治的124例烧伤增生性瘢痕患者,随机分为对照组和观察组,每组62例。对照组患者均予以序贯激光治疗,观察组在接受激光治疗后给予^(32)P同位素敷贴。比较两组患者的总有效率、瘙痒视觉模拟评分(VAS)、温哥华瘢痕量表(Vancouver scar scale,VSS)评分、简明健康状况调查量表(Short form 36 health survey,SF-36)评分、监测瘢痕组织中TGF-β_(1)、BMP-7水平及不良反应发生情况。随访6个月,观察两组患者的复发率。结果:末次治疗后,观察组患者的总有效率、SF-36评分均高于对照组(P<0.05);观察组患者的VAS评分、VSS评分均低于对照组(P<0.05);观察组患者的TGF-β_(1)水平低于对照组,BMP-7水平高于对照组(P<0.05)。两组患者在不良反应发生率方面差异无统计学意义(P>0.05)。随访6个月后,观察组患者的复发率低于对照组(P<0.05)。结论:序贯激光结合^(32)P同位素敷贴协同治疗烧伤后增生性瘢痕能够有效改善患者的临床症状和生活质量,降低复发风险,同时能够调节TGF-β_(1)和BMP-7在瘢痕形成过程中的平衡,抑制成纤维细胞增殖和胶原沉积。展开更多
Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represe...Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats.This adaptation has been hypothesized to result,in part,from the inhibition of interphalangeal cell apoptosis during limb development,although the underlying genetic mechanism remains poorly understood.This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes,BMP2,BMP4,and BMP7,which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues.Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage,with two positively selected sites(V79I and H247R)involved in cetacean-specific amino acid substitutions located in the TGF-βpropeptide functional domain in BMP4.In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors,including cytochrome c(Cyt c),BCL2 associated X,and B-cell lymphoma 2,within the BMP signaling pathway.The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.展开更多
文摘目的基于大鼠骨形态发生蛋白2(bone morphogenetic protein2,BMP2)/Smad家族成员1(smad family member 1,Smad1)通路,探究重组人转化生长因子-β1(recombinant human transforming growth factor-β1,rhTGF-β1)对正畸牙移动(orthodontic tooth movement,OMT)大鼠破骨细胞形成的影响。方法构建大鼠OTM模型,采用显微CT(Micro-CT)分析测定OTM的距离;通过抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色评估压力侧破骨细胞活性;苏木精-伊红(hematoxylin and eosin,HE)染色评估压力侧组织形态学特征,免疫组化(immunohistochemistry,IHC)染色和蛋白质印迹(Western blot)测定相关蛋白表达水平。结果与正常组相比,Model组大鼠OTM距离增加(P<0.01),牙周间隙明显变窄并出现吸收陷窝,压力侧的基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)、核因子κB受体活化因子配体(receptor activator of nuclear factor kappa B ligand,RANKL)增加(P<0.01)、骨保护素(osteoprotegerin,OPG)表达降低(P<0.01),BMP2/Smad1信号通路被激活(P<0.01)。经BMP2抑制剂Noggin处理后,与Model组相比,BMP2、p-Smad1表达显著降低(P<0.01),OTM距离显著降低(P<0.01),且压力侧的TRAP、MMP-9及RANKL表达均显著降低(P<0.01),OPG升高(P<0.01)。经rhTGF-β1处理的大鼠中,较Model组OTM距离显著增加(P<0.01),TRAP阳性多核细胞数量升高(P<0.01),压力侧的MMP-9及RANKL表达均显著升高(P<0.05)、OPG表达显著降低(P<0.01),且BMP2、p-Smad1表达上调(P<0.01)。此外,rhTGF-β1+Noggin组部分逆转了rhTGF-β1组大鼠的破骨细胞数量的增加效应(P<0.01)。结论正畸力可促进破骨细胞形成,且rhTGF-β1可通过BMP2/Smad1信号通路增强OTM过程中破骨细胞的形成。
文摘目的:探讨序贯激光结合^(32)P同位素敷贴协同治疗烧伤增生性瘢痕的疗效及对瘢痕组织TGF-β_(1)、BMP-7的影响。方法:选择2021年3月-2023年3月在笔者医院收治的124例烧伤增生性瘢痕患者,随机分为对照组和观察组,每组62例。对照组患者均予以序贯激光治疗,观察组在接受激光治疗后给予^(32)P同位素敷贴。比较两组患者的总有效率、瘙痒视觉模拟评分(VAS)、温哥华瘢痕量表(Vancouver scar scale,VSS)评分、简明健康状况调查量表(Short form 36 health survey,SF-36)评分、监测瘢痕组织中TGF-β_(1)、BMP-7水平及不良反应发生情况。随访6个月,观察两组患者的复发率。结果:末次治疗后,观察组患者的总有效率、SF-36评分均高于对照组(P<0.05);观察组患者的VAS评分、VSS评分均低于对照组(P<0.05);观察组患者的TGF-β_(1)水平低于对照组,BMP-7水平高于对照组(P<0.05)。两组患者在不良反应发生率方面差异无统计学意义(P>0.05)。随访6个月后,观察组患者的复发率低于对照组(P<0.05)。结论:序贯激光结合^(32)P同位素敷贴协同治疗烧伤后增生性瘢痕能够有效改善患者的临床症状和生活质量,降低复发风险,同时能够调节TGF-β_(1)和BMP-7在瘢痕形成过程中的平衡,抑制成纤维细胞增殖和胶原沉积。
基金supported by the National Key Programme of Research and Development,Ministry of Science and Technology of China(2022YFF1301600)National Natural Science Foundation of China(32030011,U24A20362,32070409)+2 种基金PI Project of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(GML2021 GD0805)Qing Lan Project of Jiangsu ProvincePriority Academic Program Development of Jiangsu Higher Education Institutions。
文摘Vertebrate limbs have undergone profound morphological diversification,enabling adaptations to a broad spectrum of ecological niches.In marine mammals,the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats.This adaptation has been hypothesized to result,in part,from the inhibition of interphalangeal cell apoptosis during limb development,although the underlying genetic mechanism remains poorly understood.This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes,BMP2,BMP4,and BMP7,which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues.Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage,with two positively selected sites(V79I and H247R)involved in cetacean-specific amino acid substitutions located in the TGF-βpropeptide functional domain in BMP4.In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors,including cytochrome c(Cyt c),BCL2 associated X,and B-cell lymphoma 2,within the BMP signaling pathway.The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.
