IL6ST participates in the development of adolescent idiopathic scoliosis by regulating bone marrow mesenchymal stem cells

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.