Congenital scoliosis is defined by the presence of structural anatomical malformations that arise from failures of vertebral formation or segmentation before and after birth. The understanding of genetic background and key genes for congenital scoliosis is still poor. We herein report that the excess expression of plasminogen activator inhibitor-1 (Pai-1) induced by the upregulation of miR-224-5p is involved in the pathogenesis of congenital kyphoscoliosis through impaired osteoblast differentiation. We first investigated the variety and progression of abnormalities of the lumbar spines in Ishibashi (IS) rats, a rat model of congenital kyphoscoliosis. The rats had already shown fusion and division of the primary ossification center at postnatal day 4. Over time, the rats showed various abnormalities of the lumbar spine, including the fusion of the annular epiphyseal nucleus. At postnatal day 42, spinal curvature was clearly observed due to the fusion of the vertebral bodies. Using a microRNA array, we found that the expression of miR-224-5p was increased in the lumbar spine of the rats at postnatal day 4. The expression of Pai-1, which is involved in osteoblast differentiation regulated by miR-224-5p, was also increased, while the levels of type I collagen, a marker of osteoblast differentiation, were decreased in the lumbar spine. These results indicate that the aberrant expression of miRNA-224-5p and its target genes is involved in the impaired osteoblast differentiation and may provide a partial molecular explanation for the pathogenesis of congenital scoliosis.

先天性脊柱侧弯的定义是由于出生前后椎体形成或分割失败引起的结构解剖畸形。对先天性脊柱侧弯的遗传背景和关键基因的了解仍然很差。我们在本文中报道，miR-224-5p的上调诱导的纤溶酶原激活物抑制剂1（Pai-1）的过量表达通过受损的成骨细胞分化参与了先天性脊柱后凸病的发病机理。我们首先调查了Ishibashi（IS）大鼠（一种先天性后凸性脊柱侧凸的大鼠模型）的腰椎异常的种类和进展。在出生后第4天，大鼠已经显示出原发性骨化中心的融合和分裂。随着时间的流逝，大鼠表现出各种腰椎异常，包括环状epi骨核融合。出生后第42天，由于椎体融合，清楚地观察到了脊柱弯曲。使用microRNA阵列，我们发现出生后第4天大鼠腰椎中miR-224-5p的表达增加。与miR-224-5p调控的成骨细胞分化有关的Pai-1的表达。腰椎中的，也增加了，而I型胶原（成骨细胞分化的标志物）的水平却降低了。这些结果表明，miRNA-224-5p及其靶基因的异常表达与成骨细胞分化受损有关，可能为先天性脊柱侧凸的发病机理提供了部分分子解释。由于椎体融合，可以清楚地观察到脊柱弯曲。使用microRNA阵列，我们发现出生后第4天大鼠腰椎中miR-224-5p的表达增加。与miR-224-5p调控的成骨细胞分化有关的Pai-1的表达。腰椎中的，也增加了，而I型胶原（成骨细胞分化的标志物）的水平却降低了。这些结果表明，miRNA-224-5p及其靶基因的异常表达与成骨细胞分化受损有关，可能为先天性脊柱侧凸的发病机理提供了部分分子解释。由于椎体融合，可以清楚地观察到脊柱弯曲。使用microRNA阵列，我们发现出生后第4天大鼠腰椎中miR-224-5p的表达增加。与miR-224-5p调控的成骨细胞分化有关的Pai-1的表达。腰椎中的，也增加了，而I型胶原（成骨细胞分化的标志物）的水平却降低了。这些结果表明，miRNA-224-5p及其靶基因的异常表达与成骨细胞分化受损有关，可能为先天性脊柱侧凸的发病机理提供了部分分子解释。参与miR-224-5p调节的成骨细胞分化的Pai-1的表达也增加了，而腰椎中成骨细胞分化的标志物I型胶原的水平却降低了。这些结果表明，miRNA-224-5p及其靶基因的异常表达与成骨细胞分化受损有关，可能为先天性脊柱侧凸的发病机理提供了部分分子解释。参与miR-224-5p调节的成骨细胞分化的Pai-1的表达也增加了，而腰椎中成骨细胞分化的标志物I型胶原的水平却降低了。这些结果表明，miRNA-224-5p及其靶基因的异常表达与成骨细胞分化受损有关，可能为先天性脊柱侧凸的发病机理提供了部分分子解释。