OIP5‐AS1 Sponges miR‐223‐3p to Upregulate FoxO3 and Ameliorate Temporomandibular Joint Osteoarthritis by Inhibiting Chondrocyte Apoptosis

Apoptosis and functional loss of articular chondrocytes serve as initiating events in temporomandibular joint osteoarthritis (TMJOA), and FoxO3 represents a critical molecule for sustaining chondrocyte homeostasis. This study investigates the regulatory mechanism of the lncRNA‐OIP5‐AS1/hsa‐miRNA‐223‐3p/FoxO3 axis in TMJOA, aiming to identify potential therapeutic targets for this disease. Single‐cell database analysis first revealed markedly reduced FoxO3 expression in TMJOA‐derived chondrocytes. A rat TMJOA model was then constructed and assigned to control, model, and FoxO3 overexpression groups; micro‐CT and histological staining, including HE and Safranin O‐fast green staining, were applied to assess articular cartilage injury, while immunohistochemistry was used to detect cartilage‐associated proteins Col2a1, MMP‐13, Aggrecan, and ADAMTS‐5. Further in vitro experiments validated the chondroprotective function of FoxO3 as well as the binding interaction between FoxO3 and rno‐miRNA‐223‐3p. Database screening confirmed significant down‐regulation of FoxO3 in TMJOA cartilage. Animal experiments demonstrated that FoxO3 overexpression mitigated chondrocyte injury in rat TMJOA lesions, increased Col2a1 and Aggrecan levels, and suppressed MMP‐13 and ADAMTS‐5 expression. Cellular assays showed that FoxO3 overexpression enhanced chondrocyte proliferation and matrix synthesis and preserved chondrocyte function. Sequencing and cellular evidence indicated that rno‐miRNA‐223‐3p directly targets FoxO3 mRNA to repress its transcription and negatively modulate FoxO3 abundance, consequently aggravating chondrocyte apoptosis. Collectively, rno‐miRNA‐223‐3p suppresses FoxO3 activity to facilitate TMJOA pathogenesis, and the lncRNA‐OIP5‐AS1/rno‐miRNA‐223‐3p/FoxO3 regulatory cascade may act as a promising molecular target for TMJOA clinical intervention.