类端粒沉默干扰体1(disruptor of telomeric silencing 1-like,DOT1L)是一种组蛋白H3第79位赖氨酸(H3K79)甲基转移酶,参与基因转录的表观遗传调控。近来研究发现,类端粒沉默干扰体1基因在生长板(growth plate)和关节软骨中广泛表达,并...类端粒沉默干扰体1(disruptor of telomeric silencing 1-like,DOT1L)是一种组蛋白H3第79位赖氨酸(H3K79)甲基转移酶,参与基因转录的表观遗传调控。近来研究发现,类端粒沉默干扰体1基因在生长板(growth plate)和关节软骨中广泛表达,并参与维持关节软骨稳态。全基因组关联研究(genome-wide association studies,GWAS)结果显示,类端粒沉默干扰体1基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)可增加欧洲人和中国汉族髋、膝关节骨关节炎(osteoarthritis,OA)患病风险。功能学实验证实,类端粒沉默干扰体1可下调去乙酰化酶沉默信息调节蛋白1(sirtuin-1,SIRT1)在关节软骨的表达,进而控制关节软骨内Wnt信号通路过度活化从而对关节产生保护作用;类端粒沉默干扰体1缺失可诱发小鼠和体外培养软骨细胞发生膝关节骨关节炎样改变。由此推断,调控类端粒沉默干扰体1-沉默信息调节蛋白1-Wnt信号通路网络可能是保护关节软骨、阻滞膝关节骨关节炎发生发展的有效措施。本文将在简述类端粒沉默干扰体1结构特点与活性的基础上,重点综述类端粒沉默干扰体1与膝关节骨关节炎发生发展之间的关系,以期为膝关节骨关节炎的诊治提供新靶点。展开更多
Background Articular cartilage injury is a common disease, and the incidence of articular wear, degeneration, trauma and sports injury is increasing, which often lead to disability and reduced quality of life. Unfortu...Background Articular cartilage injury is a common disease, and the incidence of articular wear, degeneration, trauma and sports injury is increasing, which often lead to disability and reduced quality of life. Unfortunately repair of articular cartilage defects do not always provide satisfactory outcomes. Methods Chondrocyte and osteoblast composites were co-cultured using a bioreactor. The cartilage defects were treated with cell-β-tricalcium phosphate （β-TCP） composites implanted into osteochondral defects in dogs, in vivo, using mosaicplasty, by placing chondrocyte-β-TCP scaffold composites on top of the defect and osteoblast-β-TCP scaffold composites below the defect.Results Electron microscopy revealed that the induced chondrocytes and osteoblast showed fine adhesive progression and proliferation in the β-TCP scaffold. The repaired tissues in the experimental group maintained their thickness to the full depth of the original defects, as compared with the negative control group （q=12.3370, P 〈0.01; q=31.5393, P 〈0.01）. Conclusions Perfusion culture provided sustained nutrient supply and gas exchange into the center of the large scaffold. This perfusion bioreactor enables the chondrocytes and osteoblasts to survive and proliferate in a three-dimensional scaffold.展开更多
文摘类端粒沉默干扰体1(disruptor of telomeric silencing 1-like,DOT1L)是一种组蛋白H3第79位赖氨酸(H3K79)甲基转移酶,参与基因转录的表观遗传调控。近来研究发现,类端粒沉默干扰体1基因在生长板(growth plate)和关节软骨中广泛表达,并参与维持关节软骨稳态。全基因组关联研究(genome-wide association studies,GWAS)结果显示,类端粒沉默干扰体1基因单核苷酸多态性(single nucleotide polymorphisms,SNPs)可增加欧洲人和中国汉族髋、膝关节骨关节炎(osteoarthritis,OA)患病风险。功能学实验证实,类端粒沉默干扰体1可下调去乙酰化酶沉默信息调节蛋白1(sirtuin-1,SIRT1)在关节软骨的表达,进而控制关节软骨内Wnt信号通路过度活化从而对关节产生保护作用;类端粒沉默干扰体1缺失可诱发小鼠和体外培养软骨细胞发生膝关节骨关节炎样改变。由此推断,调控类端粒沉默干扰体1-沉默信息调节蛋白1-Wnt信号通路网络可能是保护关节软骨、阻滞膝关节骨关节炎发生发展的有效措施。本文将在简述类端粒沉默干扰体1结构特点与活性的基础上,重点综述类端粒沉默干扰体1与膝关节骨关节炎发生发展之间的关系,以期为膝关节骨关节炎的诊治提供新靶点。
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30672116）. The authors declare that they have no competing interests.
文摘Background Articular cartilage injury is a common disease, and the incidence of articular wear, degeneration, trauma and sports injury is increasing, which often lead to disability and reduced quality of life. Unfortunately repair of articular cartilage defects do not always provide satisfactory outcomes. Methods Chondrocyte and osteoblast composites were co-cultured using a bioreactor. The cartilage defects were treated with cell-β-tricalcium phosphate （β-TCP） composites implanted into osteochondral defects in dogs, in vivo, using mosaicplasty, by placing chondrocyte-β-TCP scaffold composites on top of the defect and osteoblast-β-TCP scaffold composites below the defect.Results Electron microscopy revealed that the induced chondrocytes and osteoblast showed fine adhesive progression and proliferation in the β-TCP scaffold. The repaired tissues in the experimental group maintained their thickness to the full depth of the original defects, as compared with the negative control group （q=12.3370, P 〈0.01; q=31.5393, P 〈0.01）. Conclusions Perfusion culture provided sustained nutrient supply and gas exchange into the center of the large scaffold. This perfusion bioreactor enables the chondrocytes and osteoblasts to survive and proliferate in a three-dimensional scaffold.
