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
目的探讨髋关节发育不良(developmental dysplasia of the hip,DDH)成人患者髋臼周围骨质微结构变化及与骨质代谢相关生长因子BMP-2和Runx2(runt-related transcription factor 2)表达,分析该类患者人工全髋关节置换术后髋臼假体高松动...目的探讨髋关节发育不良(developmental dysplasia of the hip,DDH)成人患者髋臼周围骨质微结构变化及与骨质代谢相关生长因子BMP-2和Runx2(runt-related transcription factor 2)表达,分析该类患者人工全髋关节置换术后髋臼假体高松动率的原因。方法以2008年3月-9月8例行人工全髋关节置换术的DDH患者作为试验组,男3例,女5例;年龄37～55岁;髋关节脱位程度按照Crowe等评价方法评定为30%～80%。以同期8例行人工髋关节表面置换术的股骨头缺血性坏死(FicatⅡ期)患者作为对照组,男3例,女5例;年龄36～55岁。取两组患者髋臼臼顶内上方松质骨,采用实时定量PCR测量骨组织BMP-2和Runx2表达;Micro-CT扫描观察其微结构,测量骨体积分数(bone volume/total volume,BV/TV),单位体积内骨小梁分支数目(connectivity density,Conn.Dens),骨小梁数目(trabecularnumber,Tb.N),骨小梁厚度(trabecular thickness,Tb.Th),骨小梁分离度(trabecular separation,Tb.Sp),结构模型指数(structure model index,SMI)。结果试验组BMP-2及Runx2表达显著低于对照组,差异均有统计学意义(P<0.05)。Micro-CT扫描观察示,试验组骨小梁结构稀疏,单一骨小梁直径较粗,对照组骨小梁结构致密,单一骨小梁直径较细。试验组BV/TV、Tb.N显著低于对照组,SMI及Tb.Sp显著高于对照组,差异均有统计学意义(P<0.05);两组Conn.Dens及Tb.Th比较,差异无统计学意义(P>0.05)。结论 DDH患者的髋臼臼顶松质骨处于低代谢状态,其微结构趋于骨质疏松化,较差的骨质状况可能是DDH患者人工全髋关节置换术后髋臼假体高松动率的原因之一。展开更多
RUNX2是一种关键的转录因子,其在多种癌症的发生和发展中起着重要作用。由于RUNX2在多种癌症类型中对预后具有显著的影响,其作为癌症生物标志物的潜力引起了广泛关注。RUNX2通过与核心结合因子β (CBFβ)结合,增强对靶基因的调控,促进...RUNX2是一种关键的转录因子,其在多种癌症的发生和发展中起着重要作用。由于RUNX2在多种癌症类型中对预后具有显著的影响,其作为癌症生物标志物的潜力引起了广泛关注。RUNX2通过与核心结合因子β (CBFβ)结合,增强对靶基因的调控,促进癌细胞的增殖、迁移和侵袭。RUNX2与PI3K/AKT信号通路互作,激活肿瘤进展的关键途径。抑制RUNX2的表达和功能已显示出抑制肿瘤生长和迁移、促进癌细胞凋亡的潜力,使其成为癌症治疗中的有意义靶标。近年研究还发现,RUNX2影响肿瘤微环境和化疗耐药性,针对RUNX2的小分子抑制剂和靶向疗法的开发,为提高治疗效果和减少耐药现象提供了新的策略。RUNX2 is a critical transcription factor that plays an important role in the initiation and progression of various cancers. Due to its significant impact on prognosis across multiple cancer types, RUNX2 has garnered widespread attention as a potential biomarker for cancer. By interacting with core-binding factor β (CBFβ), RUNX2 enhances the regulation of target genes, promoting cancer cell proliferation, migration, and invasion. RUNX2 also interacts with the PI3K/AKT signaling pathway, activating key pathways involved in tumor progression. Inhibiting RUNX2 expression and function has demonstrated potential in suppressing tumor growth and migration, as well as inducing apoptosis in cancer cells, making it a meaningful therapeutic target in cancer treatment. Recent studies have also revealed that RUNX2 influences the tumor microenvironment and chemotherapy resistance. The development of small molecule inhibitors and targeted therapies against RUNX2 offers novel strategies to improve therapeutic efficacy and reduce resistance.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RUNX2是一种关键的转录因子,其在多种癌症的发生和发展中起着重要作用。由于RUNX2在多种癌症类型中对预后具有显著的影响,其作为癌症生物标志物的潜力引起了广泛关注。RUNX2通过与核心结合因子β (CBFβ)结合,增强对靶基因的调控,促进癌细胞的增殖、迁移和侵袭。RUNX2与PI3K/AKT信号通路互作,激活肿瘤进展的关键途径。抑制RUNX2的表达和功能已显示出抑制肿瘤生长和迁移、促进癌细胞凋亡的潜力,使其成为癌症治疗中的有意义靶标。近年研究还发现,RUNX2影响肿瘤微环境和化疗耐药性,针对RUNX2的小分子抑制剂和靶向疗法的开发,为提高治疗效果和减少耐药现象提供了新的策略。RUNX2 is a critical transcription factor that plays an important role in the initiation and progression of various cancers. Due to its significant impact on prognosis across multiple cancer types, RUNX2 has garnered widespread attention as a potential biomarker for cancer. By interacting with core-binding factor β (CBFβ), RUNX2 enhances the regulation of target genes, promoting cancer cell proliferation, migration, and invasion. RUNX2 also interacts with the PI3K/AKT signaling pathway, activating key pathways involved in tumor progression. Inhibiting RUNX2 expression and function has demonstrated potential in suppressing tumor growth and migration, as well as inducing apoptosis in cancer cells, making it a meaningful therapeutic target in cancer treatment. Recent studies have also revealed that RUNX2 influences the tumor microenvironment and chemotherapy resistance. The development of small molecule inhibitors and targeted therapies against RUNX2 offers novel strategies to improve therapeutic efficacy and reduce resistance.
