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首页> 外文期刊>Molecular and Cellular Biology >Mice with a Disruption of the Thrombospondin 3 Gene Differ in Geometric and Biomechanical Properties of Bone and Have Accelerated Development of the Femoral Head
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Mice with a Disruption of the Thrombospondin 3 Gene Differ in Geometric and Biomechanical Properties of Bone and Have Accelerated Development of the Femoral Head

机译:破坏血小板反应蛋白3基因的小鼠的骨几何和生物力学特性不同,并加速了股骨头的发育

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Thrombospondin 3 (TSP3) is structurally similar to cartilage oligomeric matrix protein (COMP/TSP5), but its function is unknown. To determine the functional significance of TSP3, we generated mice with a targeted disruption of Thbs3. TSP3-null mice are viable and fertile and show normal prenatal skeletal patterning, based on Alcian blue/Alizarin red S staining. However, subtle and transient abnormalities were detected in the developing postnatal skeleton. Young adult TSP3-null mice are heavier than controls, and analyses of the geometric and biomechanical properties of long bones show increases in the moments of inertia, endocortical and periostal radii, and failure load. The bones of 9-week-old TSP3-null male mice also have a significantly greater cortical area. Most of these differences were no longer detected in 15-week-old mice. Microcomputed tomography scans showed that the trabecular bone proximal to the femoral head growth plate developed at an earlier time in TSP3-null mice than in wild-type mice. Thus, vascular invasion and ossification start in the femoral heads of TSP3-null mice at 9 weeks, whereas the wild-type femoral head is still composed of hypertrophic chondroctyes in a calcified matrix at 15 weeks. These results provide evidence for a role for TSP3 in the regulation of skeletal maturation in mice.
机译:血小板反应蛋白3(TSP3)在结构上类似于软骨寡聚基质蛋白(COMP / TSP5),但其功能尚不清楚。为了确定TSP3的功能意义,我们生成了具有针对性破坏 Thbs3 的小鼠。基于Alcian蓝/ Alizarin红S染色,TSP3无效的小鼠具有活力和繁殖力,并显示正常的产前骨骼模式。然而,在发育中的产后骨骼中发现了细微和短暂的异常。成年TSP3空小鼠比对照组重,对长骨的几何和生物力学特性的分析表明,惯性矩,皮质内和牙周膜半径以及失效载荷增加。 9周龄无TSP3的雄性小鼠的骨骼也具有明显更大的皮质区域。在15周龄的小鼠中不再检测到大多数这些差异。显微计算机断层扫描显示,TSP3空小鼠的股骨头生长板近端骨小梁比野生型小鼠早。因此,在9周时,TSP3空小鼠的股骨头开始出现血管浸润和骨化,而在15周时,野生型股骨头仍由钙化基质中的肥大软骨素组成。这些结果提供了TSP3在调节小鼠骨骼成熟中的作用的证据。

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