Tight-skin （TSK） mice are commonly used as an animal model to study the pathogenesis of Marfan syndrome （MFS）, but little is known of their skeletal phenotype and in particular of the development of the spinal def...Tight-skin （TSK） mice are commonly used as an animal model to study the pathogenesis of Marfan syndrome （MFS）, but little is known of their skeletal phenotype and in particular of the development of the spinal deformities, common in MFS. Here we examined growth of the axial skeletons of TSK and wild-type（B6） mice during their period of rapid growth. The whole bodies of mice, 4-12 weeks of age, were scanned after sacrifice, by micro-computed tomography （microCT）. We reconstructed three-dimensional models of the spine and ribs, and measured vertebral body heights and rib lengths using the Mac-based image-processing software ＂OsiriX＂. Although the TSK mice were smaller than the B6 mice at 4 weeks, they experienced an early growth spurt and by 8 weeks the height, but not the width, of the vertebral body was significantly greater in the TSK mice than the B6 mice. Measurement of the angles of scoliotic and kyphotic curves postmortem in the mice was problematic, hence we measured changes that develop in skeletal elements in these disorders. As a marker of kyphosis, we measured anterior wedging of the vertebral bodies; as a marker for scoliosis we measured asymmetries in rib length. We found, unlike in the B6 mice where the pattern was diffuse, wedging in TSK mice was directly related to spinal level and peaked steeply at the thoracolumbar junction. There was also significant asymmetry in length of the ribs in the TSK mice, but not in the B6 mice. The TSK mice thus appear to exhibit spinal deformities seen in MFS and could be a useful model for gaining understanding of the mechanisms of development of scoliosis and kyphosis in this disorder.展开更多
丝素蛋白是一种从蚕丝中提取的天然高分子纤维蛋白,有很好的抗氧化和减少光损伤的作用。为了研究丝素蛋白对皮肤光损伤的保护作用,以UVB诱导人角质形成细胞(HaCaT)损伤为模型,通过ELISA和荧光检测细胞内活性氧(ROS)和钙离子(Ca^(2+))的...丝素蛋白是一种从蚕丝中提取的天然高分子纤维蛋白,有很好的抗氧化和减少光损伤的作用。为了研究丝素蛋白对皮肤光损伤的保护作用,以UVB诱导人角质形成细胞(HaCaT)损伤为模型,通过ELISA和荧光检测细胞内活性氧(ROS)和钙离子(Ca^(2+))的水平,采用免疫荧光检测瞬时受体电位阳离子通道亚家族V成员1(TRPV1)和Claudin-1的表达。此外,还使用蛋白质印迹分析了紧密连接相关蛋白Occludin和Claudin-1的表达。结果表明,120 m J/cm^(2)的UVB刺激显著降低细胞活力,而100μg/m L丝素蛋白的存在显著增加细胞活力。UVB刺激导致细胞内活性氧水平升高,激活TRPV1通道,诱导细胞内Ca^(2+)水平增加。同时炎症因子白细胞介素1α(IL-1α)(P<0.01)和S100钙结合蛋白A8(S100A8)(P<0.05)水平也显著升高,引发炎症反应。添加丝素蛋白的HaCaT细胞受到UVB的影响则显著降低(P<0.05)。实验证明,UVB会破坏屏障蛋白,导致屏障蛋白Claudin-1和Occludin的表达下降。丝素蛋白的加入可以降低这种影响,保护细胞间紧密连接。因此,丝素蛋白可能具有降低氧化应激、屏障损伤和炎症发生,保护皮肤免受UVB诱导的光损伤的潜在能力。展开更多
基金funding for support of this research from the British Scoliosis Research Foundation (JU, JY)the China Postdoctoral Science Foundation (2012M520584)Tianjin Postdoctoral Science Foundation (BL)
文摘Tight-skin （TSK） mice are commonly used as an animal model to study the pathogenesis of Marfan syndrome （MFS）, but little is known of their skeletal phenotype and in particular of the development of the spinal deformities, common in MFS. Here we examined growth of the axial skeletons of TSK and wild-type（B6） mice during their period of rapid growth. The whole bodies of mice, 4-12 weeks of age, were scanned after sacrifice, by micro-computed tomography （microCT）. We reconstructed three-dimensional models of the spine and ribs, and measured vertebral body heights and rib lengths using the Mac-based image-processing software ＂OsiriX＂. Although the TSK mice were smaller than the B6 mice at 4 weeks, they experienced an early growth spurt and by 8 weeks the height, but not the width, of the vertebral body was significantly greater in the TSK mice than the B6 mice. Measurement of the angles of scoliotic and kyphotic curves postmortem in the mice was problematic, hence we measured changes that develop in skeletal elements in these disorders. As a marker of kyphosis, we measured anterior wedging of the vertebral bodies; as a marker for scoliosis we measured asymmetries in rib length. We found, unlike in the B6 mice where the pattern was diffuse, wedging in TSK mice was directly related to spinal level and peaked steeply at the thoracolumbar junction. There was also significant asymmetry in length of the ribs in the TSK mice, but not in the B6 mice. The TSK mice thus appear to exhibit spinal deformities seen in MFS and could be a useful model for gaining understanding of the mechanisms of development of scoliosis and kyphosis in this disorder.
文摘丝素蛋白是一种从蚕丝中提取的天然高分子纤维蛋白,有很好的抗氧化和减少光损伤的作用。为了研究丝素蛋白对皮肤光损伤的保护作用,以UVB诱导人角质形成细胞(HaCaT)损伤为模型,通过ELISA和荧光检测细胞内活性氧(ROS)和钙离子(Ca^(2+))的水平,采用免疫荧光检测瞬时受体电位阳离子通道亚家族V成员1(TRPV1)和Claudin-1的表达。此外,还使用蛋白质印迹分析了紧密连接相关蛋白Occludin和Claudin-1的表达。结果表明,120 m J/cm^(2)的UVB刺激显著降低细胞活力,而100μg/m L丝素蛋白的存在显著增加细胞活力。UVB刺激导致细胞内活性氧水平升高,激活TRPV1通道,诱导细胞内Ca^(2+)水平增加。同时炎症因子白细胞介素1α(IL-1α)(P<0.01)和S100钙结合蛋白A8(S100A8)(P<0.05)水平也显著升高,引发炎症反应。添加丝素蛋白的HaCaT细胞受到UVB的影响则显著降低(P<0.05)。实验证明,UVB会破坏屏障蛋白,导致屏障蛋白Claudin-1和Occludin的表达下降。丝素蛋白的加入可以降低这种影响,保护细胞间紧密连接。因此,丝素蛋白可能具有降低氧化应激、屏障损伤和炎症发生,保护皮肤免受UVB诱导的光损伤的潜在能力。
