Liang Zhuo-Tao, Tang Hao, Li Jiong, Li Jia-Ke, Rong Rong, Jiang Zhong-Jing, Li Meng-Jun, Tang Ming-Xing, Zhang Hong-Qi
Department of Spine Surgery and Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
Commun Biol. 2025 Sep 26;8(1):1369. doi: 10.1038/s42003-025-08746-w.
Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spinal deformity that primarily affects adolescents, and its pathogenesis remains elusive. Several studies have indicated that AIS may be associated with low bone mineral density, and bone marrow mesenchymal stem cells (BMSCs) are known to play a crucial role in bone metabolism. Through high-throughput sequencing of the BMSC transcriptome, we identified 1919 differentially expressed genes and pinpointed IL6ST as a key gene influencing osteogenic differentiation in AIS. Mechanistic experiments revealed that IL6ST regulates the osteogenic differentiation of BMSCs by activating the JAK/STAT3/RANKL/OPG pathway. Moreover, knockout of IL6ST expression significantly increased the malformation rate in zebrafish models. We further explored upstream regulators of IL6ST. Using high-throughput sequencing and bioinformatics analysis, we identified CircSCAF8 as a potential upstream regulatory circRNA of IL6ST. Collectively, these findings suggest that IL6ST may be a pivotal gene in the development of AIS, deepening our understanding of its pathogenesis.
青少年特发性脊柱侧凸（AIS）是一种主要影响青少年的复杂三维脊柱畸形，其发病机制仍不清楚。多项研究表明，AIS可能与低骨密度有关，并且已知骨髓间充质干细胞（BMSC）在骨代谢中起关键作用。通过对BMSC转录组进行高通量测序，我们鉴定出1919个差异表达基因，并确定IL6ST是影响AIS中成骨分化的关键基因。机制实验表明，IL6ST通过激活JAK/STAT3/RANKL/OPG途径调节BMSC的成骨分化。此外，敲除IL6ST表达显著增加了斑马鱼模型中的畸形率。我们进一步探索了IL6ST的上游调节因子。通过高通量测序和生物信息学分析，我们确定CircSCAF8是IL6ST潜在的上游调节环状RNA。总的来说，这些发现表明IL6ST可能是AIS发展中的关键基因，加深了我们对其发病机制的理解。
