miRNA-130b-3p upregulation impairs osteogenic differentiation in AIS patients by inhibiting the IGF1/ERK pathway.

Abstract

Adolescents with idiopathic scoliosis (AIS) often exhibit a slender body shape and reduced bone mass, even in the absence of evident vertebral deformities. Although prior studies have implicated microRNAs (miRNAs) in the development and progression of AIS, the precise mechanisms remain poorly understood. Therefore, primary osteoblasts and plasma samples from AIS patients and controls were isolated and associated mechanism was investigated in this study. We observed impaired osteogenic capacity of AIS-osteoblasts, and further identified a significant elevation of miRNA-130b-3p in AIS patients compared to controls through RNA sequencing of plasma samples. The expression levels of miR-130b-3p were validated in an independent cohort of 40 individuals using qPCR. Dual-energy X-ray absorptiometry showed reduced bone mineral density (BMD) in AIS patients. And the correlation analysis revealed a significant negative relationship between miR-130b-3p levels and BMD. Additionally, transcriptomic analysis and dual-luciferase assays confirmed that overexpression of miR-130b-3p in primary osteoblasts inhibited the activation of the ERK1/2 signaling pathway by targeting IGF1, thereby disrupting bone metabolism. Meanwhile, knockdown of miR-130b-3p in AIS-derived osteoblasts improved osteogenic function. In zebrafish, miR-130b-3p overexpression delayed vertebral development and induced spinal deformities. In summary, this study identifies a significant increase of miR-130b-3p in AIS patients and demonstrates its role in impairing osteogenic function through suppression of the IGF1/ERK signaling pathway.