The potential involvement of FABP4 in rheumatoid arthritis-associated osteoporosis: a comprehensive bioinformatics analysis and experimental validation

ObjectiveThis study investigates the role and underlying mechanism of FABP4 in RA secondary OP by examining its correlation with the condition.MethodsDEGs related to RA and OP were identified using GEO datasets (GSE17755 and GSE230665), focusing on bone metabolism genes. Candidate genes were identified using WGCNA, PPI networks, and four algorithms (Degree, BottleNeck, MCC, EPC), followed by enrichment analysis.

Key genes were pinpointed using machine learning methods (SVM-RFE, LASSO, Boruta) and validated with ROC curves, all showing AUC > 0.7. MicroRNA prediction and genomic mapping were also done.

For in vivo validation, CIA rats (n=5 per group) were analyzed at 2, 6, and 12 weeks against a control group using ELISA, micro-CT, H&E staining, IHC, and quantitative image analysis.ResultsBioinformatics identified eight hub genes: PTEN, CDC42, MFN2, UBC, RAS5F1, MMP9, CCL17, and FABP4. In CIA rats, FABP4, TNF-α, IL-6, IL-1β, RANKL, and β-CTX levels rose with disease progression, showing slight increases at 2 weeks and significant rises at 6 and 12 weeks (P<0.05).

At 12 weeks, these levels were higher than at 6 weeks (P<0.01).