青少年特发性脊柱侧凸（AIS）是一种好发于青春期的常见脊柱慢性疾病。我们先前通过全基因组关联分析研究定位了与汉族AIS发病相关的数个重要易感基因，其中LBX1基因，PAX3基因，和TNIK基因均位于Wnt/β-catenin通路。在对AIS患者两侧椎旁肌的基因表达进行分析后，我们发现AIS患者PAX3以及LBX1的mRNA和蛋白表达较正常人均有显著下降，同时在脊柱凹凸两侧也存在显著表达差异。而其下游基因MyoD表达变化可能导致的肌纤维分布异常亦在AIS患者得到初步证实。因此，我们推断AIS患者MyoD基因受Wnt/β-catenin信号通路基因调控。同时该通路可能影响肌肉和骨骼发育的相互作用，进而参与AIS发病过程。本项目将首次通过细胞学实验和动物模型探索Wnt/β-catenin信号通路基因异常表达对AIS患者椎旁肌发育的调控作用。上述研究成果将进一步揭示AIS发生和进展的分子机制。

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity that occurs in the puberty. We have previously identified several important susceptibility genes related to AIS by genome wide association analysis, of which LBX1, PAX3 and TNIK genes are all located in the Wnt/beta-catenin signal pathway. After analyzing the gene expression of bilateral paraspinal muscles in AIS patients, we found that PAX3 and LBX1 are remarkably down-expressed in AIS patients than in normal controls. Besides, there were significant differences between the concave and the convex side regarding the gene expression. The abnormality of the muscle fiber distribution was also observed in the patients with down-expressed MyoD. Therefore, we speculated that the MyoD gene may be regulated by the Wnt/beta-catenin signaling pathway in AIS patients, which in turn influenced the distribution of muscle fiber in the bilateral paraspinal muscles. Meanwhile, the Wnt/beta-catenin pathway may affect the interaction between muscle and bone development. This project aims to investigate the regulation of asymmetric expression of the Wnt/beta-catenin pathway gene and to clarify its role in the development of bilateral paraspinal muscles in AIS patients through cytological experiments and animal models. Our results will further reveal the molecular mechanism underlying the occurrence and progression of AIS.