Post-Transcriptional Regulator RBM47 Stabilizes FBXO2 mRNA to Advance Osteoarthritis Development: WGCNA Analysis and Experimental Validation.

Osteoarthritis (OA) is a common chronic joint degenerative disease and a major cause of disability in the elderly. However, the current intervention strategies cannot effectively improve OA, and the pathogenesis of OA remains elusive. The present study identified RNA binding motif protein 47 (RBM47) as an upstream modulator of key dysregulation gene co-expression module based on weighted gene co-expression network analysis (WGCNA) analysis and least absolute shrinkage and selection operator (Lasso) modeling. Subsequently, data from real-time quantitative PCR and western blot analysis revealed that RBM47 was upregulated in OA models in vivo and in vitro compared with normal controls. Functional analysis results from the MTT assay, flow cytometry, evaluation of LDH activities and inflammatory mediators, and western blot analysis of extracellular matrix (ECM) proteins, showed that RBM47 knockdown significantly alleviated inflammation, apoptosis, and ECM degradation in interleukin 1β (IL-1β)-treated chondrocytes. Mechanistically, RBM47 bound to F box only protein 2 (FBXO2) and stabilized FBXO2 messenger RNA (mRNA) to promote the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in chondrocytes. Results from the recovery assay showed that the re-activation of STAT3 signaling by overexpressing FBXO2 or STAT3 counteracted the alleviating effect of RBM47 downregulation on IL-1β-induced inflammation, apoptosis, and ECM degradation. Altogether, our findings illustrate that RBM47 stabilizes FBXO2 mRNA to advance OA development by activating STAT3 signaling, which enhances our understanding of the molecular regulatory mechanisms underlying the development of OA.