OIP5-AS1 Sponges miR-223-3p to Upregulate FoxO3 and Ameliorate Temporomandibular Joint Osteoarthritis by Inhibiting...

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.