目的探讨广东省一个汉族A1型短指(brachydactyly type A1)家系的临床特征及致病原因。方法在获得知情同意后对该家系成员进行病史采集和临床检测,并对其中7例患者和7例正常亲属采血进行DNA提取,采用聚合酶链反应结合DNA直接测序法对IHH...目的探讨广东省一个汉族A1型短指(brachydactyly type A1)家系的临床特征及致病原因。方法在获得知情同意后对该家系成员进行病史采集和临床检测,并对其中7例患者和7例正常亲属采血进行DNA提取,采用聚合酶链反应结合DNA直接测序法对IHH基因的外显子进行突变检测。结果该家系的短指症为A1型,常染色体显性遗传;所有患者第二至第五手指和脚趾的中节指(趾)骨缺失,末节指(趾)骨短小,第一手指的远侧和近侧指骨均缩短;7例患者在IHH基因对应cDNA序列存在G391A(E131K)杂合突变,7例正常亲属均未发现该突变。结论中国广东汉族A1型短指家系的发病机制是IHH基因发生了E131K错义突变所致。展开更多
目的:评价肥胖相关基因(fat mass and obesity associated gene,FTO)蛋白在人甲状腺乳头状癌IHH-4细胞中的表达、生物学作用及18α-甘草次酸(18α-Glycyrrhetinic acid,AGA)对该细胞FTO表达的影响。方法:体外培养IHH-4细胞,取对数生长...目的:评价肥胖相关基因(fat mass and obesity associated gene,FTO)蛋白在人甲状腺乳头状癌IHH-4细胞中的表达、生物学作用及18α-甘草次酸(18α-Glycyrrhetinic acid,AGA)对该细胞FTO表达的影响。方法:体外培养IHH-4细胞,取对数生长期细胞进行实验;采用MTT和Transwell迁移实验评价不同浓度的AGA(80、160、320μmol/L)对IHH-4细胞增殖和迁移能力的影响;通过RNA干扰(RNA interference,RNAi)技术沉默肥胖相关基因(fat mass and obesity associated gene,FTO)的表达;采用Western blot法评价AGA处理前后FTO、周期蛋白依赖性激酶4(cyclin-dependent kinase 4,CDK4)和Cofilin-1的表达。结果:不同浓度的AGA均能显著抑制IHH-4细胞的增殖及迁移,差异具有统计学意义(P<0.05);IHH-4细胞高表达FTO、CDK4和Cofilin-1;RNAi下调IHH-4细胞FTO后导致CDK4和Cofilin-1表达水平显著降低(P<0.05),IHH-4细胞的增殖及迁移能力亦显著下降;AGA处理显著减少了IHH-4细胞中FTO、CDK4和Cofilin-1的表达水平(P<0.05);经RNAi处理48 h的IHH-4细胞再加入AGA无法进一步降低FTO、CDK4和Cofilin-1的表达水平及增殖、迁移能力(P>0.05)。结论:FTO在促进人甲状腺乳头状癌细胞的增殖及迁移中具有重要作用;AGA通过控制FTO的表达抑制IHH-4细胞的增殖及迁移。展开更多
Indian hedgehog （Ihh） is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression ...Indian hedgehog （Ihh） is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh-/- mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh-/- mouse, but failed to restore orthotopic osteoblast differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh-/-; Gli3-/- embryo. Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development.展开更多
文摘目的探讨广东省一个汉族A1型短指(brachydactyly type A1)家系的临床特征及致病原因。方法在获得知情同意后对该家系成员进行病史采集和临床检测,并对其中7例患者和7例正常亲属采血进行DNA提取,采用聚合酶链反应结合DNA直接测序法对IHH基因的外显子进行突变检测。结果该家系的短指症为A1型,常染色体显性遗传;所有患者第二至第五手指和脚趾的中节指(趾)骨缺失,末节指(趾)骨短小,第一手指的远侧和近侧指骨均缩短;7例患者在IHH基因对应cDNA序列存在G391A(E131K)杂合突变,7例正常亲属均未发现该突变。结论中国广东汉族A1型短指家系的发病机制是IHH基因发生了E131K错义突变所致。
文摘目的:评价肥胖相关基因(fat mass and obesity associated gene,FTO)蛋白在人甲状腺乳头状癌IHH-4细胞中的表达、生物学作用及18α-甘草次酸(18α-Glycyrrhetinic acid,AGA)对该细胞FTO表达的影响。方法:体外培养IHH-4细胞,取对数生长期细胞进行实验;采用MTT和Transwell迁移实验评价不同浓度的AGA(80、160、320μmol/L)对IHH-4细胞增殖和迁移能力的影响;通过RNA干扰(RNA interference,RNAi)技术沉默肥胖相关基因(fat mass and obesity associated gene,FTO)的表达;采用Western blot法评价AGA处理前后FTO、周期蛋白依赖性激酶4(cyclin-dependent kinase 4,CDK4)和Cofilin-1的表达。结果:不同浓度的AGA均能显著抑制IHH-4细胞的增殖及迁移,差异具有统计学意义(P<0.05);IHH-4细胞高表达FTO、CDK4和Cofilin-1;RNAi下调IHH-4细胞FTO后导致CDK4和Cofilin-1表达水平显著降低(P<0.05),IHH-4细胞的增殖及迁移能力亦显著下降;AGA处理显著减少了IHH-4细胞中FTO、CDK4和Cofilin-1的表达水平(P<0.05);经RNAi处理48 h的IHH-4细胞再加入AGA无法进一步降低FTO、CDK4和Cofilin-1的表达水平及增殖、迁移能力(P>0.05)。结论:FTO在促进人甲状腺乳头状癌细胞的增殖及迁移中具有重要作用;AGA通过控制FTO的表达抑制IHH-4细胞的增殖及迁移。
基金supported by NIH grants R01 DK065789 and R01 AR060456 to FL
文摘Indian hedgehog （Ihh） is an essential signal that regulates endochondral bone development. We have previously shown that Wnt7b promotes osteoblast differentiation during mouse embryogenesis, and that its expression in the perichondrium is dependent on Ihh signaling. To test the hypothesis that Wnt7b may mediate some aspects of Ihh function during endochondral bone development, we activated Wnt7b expression from the R26-Wnt7b allele with Col2-Cre in the Ihh-/- mouse. Artificial expression of Wnt7b rescued vascularization of the hypertrophic cartilage in the Ihh-/- mouse, but failed to restore orthotopic osteoblast differentiation in the perichondrium. Similarly, Wnt7b did not recover Ihh-dependent perichondral bone formation in the Ihh-/-; Gli3-/- embryo. Interestingly, Wnt7b induced bone formation at the diaphyseal region of long bones in the absence of Ihh, possibly due to increased vascularization in the area. Thus, Ihh-dependent expression of Wnt7b in the perichondrium may contribute to vascularization of the hypertrophic cartilage during endochondral bone development.
