汉黄胆素通过调控软骨细胞中COL1A2的表达，缓解白介素-1β诱导的炎症、细胞凋亡、氧化应激及细胞外基质降解反应。

Abstract

Background Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by progressive cartilage destruction. Interleukin-1β (IL-1β) is a pivotal pro-inflammatory cytokine that drives OA pathogenesis by inducing chondrocyte injury. Investigating targeted interventions to mitigate IL-1β-induced chondrocyte damage is crucial for OA treatment. Baicalin, a naturally active flavonoid, has demonstrated potent anti-inflammatory and antioxidant properties. However, the precise molecular mechanisms by which baicalin modulates IL-1β-induced chondrocyte injury to retard OA progression remain largely elusive and warrant comprehensive investigation. Methods Differentially expressed genes (DEGs) between OA and normal cartilage tissues were identified from the GSE169077 dataset. The overlapping genes between these DEGs and the predicted baicalin targets were subjected to machine learning algorithms, specifically support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF), to pinpoint the pivotal hub gene. Gene set enrichment analysis (GSEA) was utilized to evaluate the biological functions of the hub gene. Subsequently, in vitro chondrocyte models were established by IL-1β exposure, followed by baicalin treatment and/or hub gene overexpression. Results Bioinformatics analysis revealed significant DEGs in OA cartilage, primarily enriched in ECM organization and the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. By intersecting baicalin targets with DEGs and applying SVM-RFE and RF algorithms, collagen type I alpha 2 chain (COL1A2) was identified as the hub gene and was found to be highly expressed in OA specimens. Functional assays demonstrated that IL-1β stimulation robustly elevated COL1A2 protein expression by 2.66-fold ( P  < 0.0001), exacerbated chondrocyte apoptosis by 3.24-fold ( P  < 0.0001), upregulated pro-apoptotic proteins (Bax by 1.66-fold and cleaved caspase 3 by 2.00-fold, P  < 0.0001), and downregulated anti-apopt