Cerium Nanozymes Synergizing Imt1 Block Dsrna Inflammation In Tmjoa

Emerging evidence suggests mitochondrial double-stranded RNAs (dsRNAs) act as critical inflammatory mediators by triggering downstream proinflammatory cascades, potentially driving temporomandibular joint osteoarthritis (TMJOA) pathogenesis. dsRNA accumulation in LPS-stimulated bone marrow-derived macrophages (BMDMs) and CFA-induced TMJOA rats (male, 8-week-old) was confirmed via immunofluorescence (IF) and immunohistochemistry (IHC). A cerium-based meso-porous silicon co-loaded with IMT1 (Ce@MSN-IMT1) was synthesized to simultaneously suppress dsRNA generation and enhance its hydrolysis. In vitro, the expression of dsRNA, inflammatory factors and receptor proteins (IL-18, IL-1β, RIG-I, MDA5) were analyzed by IF, Western blot (WB), and qPCR. For in vivo evaluation, CFA-induced TMJOA rats (randomized into Sham, Control, IMT1, Cerium Nanozyme, and Combination groups) underwent synovial inflammation assessment via H&E staining, ELISA test and dsRNA quantification after 4 weeks administration. All protocols were approved by the Institutional Animal Ethics Committee. Ce@MSN-IMT1 effectively reduced dsRNA accumulation in LPS-treated BMDMs and inflamed joint. WB, qPCR and IF revealed synergistic inhibition of dsRNA-RIG-I/MDA5 pathways and proinflammatory cytokines. H&E staining and ELISA confirmed Ce@MSN-IMT1 attenuated synovial inflammation better than monotherapy. Mitochondrial dsRNA is a pivotal driver of TMJOA progression. Ce-IMT1 nanozymes demonstrate dual-action efficacy by concurrently modulating dsRNA biogenesis and hydrolysis, offering a promising strategy to mitigate inflammatory cascades and improve TMJOA outcomes.