青少年特发性脊柱侧凸（AIS）是一组病因不明的脊柱三维畸形，常累及处于青春期的患儿，发病率在1-4%之间。申请人前期研究报道AIS骨组织微结构、矿化及力学强度的异常与骨细胞Wnt-β-catenin通路调控异常密切相关。我们预实验发现AIS脊柱骨细胞陷窝-微管系统（LCS）超微结构异常，Wnt通路中Lrp6表达增加，可直接抑制Lrp6的miR-96-5p表达明显降低，但具体调控机制不明确。本项目在前期工作基础上扩大临床样本量，证明AIS骨细胞LCS超微结构及LCS旁矿化异常的病理学改变。构建原代骨细胞miR-96-5p过表达及敲低细胞模型，研究AIS的Wnt-Lrp6-β-catenin通路调控机制与LCS结构异常形成的机制。通过分析AIS侧凸进展患者与非进展患者血浆miR-96-5p表达水平，明确miR-96-5p作为早期预判侧凸进展的外周血标记物的潜在临床价值，为临床干预提供新思路。

Adolescent idiopathic scoliosis (AIS) is the three-dimensional spinal deformity occurring mostly in adolescent during pubertal growth with a prevalence rate of 1-4% worldwide. The etiopathogenesis of AIS remains largely unknow. In our previous publication, the abnormal bone microstructure with less mineralization and poor mechanical property in AIS bone tissue associated with abnormal regulation of Wnt-β-catenin pathway in osteocytes. Our pilot study demonstrated that the abnormal osteocytes lacuno-canalicular system (LCS), the higher expression of Lrp6 mRNA and lower expression of miR-96-5p were in AIS bone tissue. But, the mechanism of the regulation remains unknow. With our recent pilot data and the coming larger sample size, the first objective of this study is to confirm the ultrastructural changes of osteocyte LCS and the low mineral content of peri-lacunar area in AIS spinal and iliac bone tissue. Based on the miR-96-5p overexpression/knockdown cellular model in the primary osteocytes culture, this case-control study aimed to explore the mechanisms of Wnt-Lrp6-β-catenin pathway and the pathogenic mechanisms of the osteocytes LCS malformation in AIS. To compare the plasma miR-96-5p expression level between the progressive group and stable group from AIS, this study will shed light on the potential clinical significance of the circulating miR-96-5p in predicting AIS curve progression in the early stage and in creating the new ideas for the treatment.