Multimodal analysis investigating the shared pathogenic mechanisms of osteoporosis and osteoarthritis with an initial exploration of the role of ferroptosis.

Abstract

BACKGROUND: Osteoarthritis (OA) and osteoporosis (OP) are prevalent conditions with overlapping molecular mechanisms. Recent studies have brought attention to ferroptosis, a type of cell death that relies on iron, as a possible connection between these diseases. METHODS: We performed a comprehensive analysis with datasets obtained from the Gene Expression Omnibus (GEO), focusing on differentially expressed genes (DEGs) in OA and OP. Functional enrichment and integrated analyses identified ferroptosis-related pathways. The role of ferroptosis in OP was further explored through in vivo studies using an ovariectomy-induced OP mouse model. RESULTS: The analysis revealed significant overlaps in DEGs related to ferroptosis pathways in both OA and OP. Key genes like TXNIP and SLC2A3 were implicated in the regulation of ferroptosis and associated with disease mechanisms. In vivo results confirmed increased ferroptosis markers in bone marrow stromal cells (BMSCs) from OP mice, supporting the hypothesis that ferroptosis contributes to bone density reduction and structural deterioration. CONCLUSION: Our findings highlight ferroptosis as a critical pathway in the pathogenesis of both OA and OP. Targeting ferroptosis-related genes and pathways could provide new therapeutic opportunities for managing these musculoskeletal diseases.