Dexamethasone Liposomes Alleviate Osteoarthritis in miR-204/-211-Deficient Mice by Repolarizing Synovial Macrophages to M2 Phenotypes

We undertook this study to investigate the effects andmechanismsof dexamethasone liposome (Dex-Lips) on alleviating destabilizationof the medial meniscus (DMM)-induced osteoarthritis (OA) in miR-204/-211-deficientmice. Dex-Lips was prepared by the thin-film hydration method. Thecharacterization of Dex-Lips was identified by the mean size, zetapotential, drug loading, and encapsulation efficiencies. ExperimentalOA was established by DMM surgery in miR-204/-211-deficient mice,and then Dex-Lips was treated once a week for 3 months. Von Frey filamentswas used to perform the pain test. The inflammation level was evaluatedwith quantitative real-time polymerase chain reaction and enzyme-linkedimmunosorbent assay. Polarization of macrophages was evaluated byimmunofluorescent staining. X-ray, micro-CT scanning, and histologicalobservations were conducted in vivo on DMM mice to describe the OAphenotype. We found that miR-204/-211-deficient mice displayed moresevere OA symptoms than WT mice after DMM surgery. Dex-Lips amelioratedDMM-induced OA phenotype and suppressed pain and inflammatory cytokineexpressions. Dex-Lips could attenuate pain by regulating PGE2. Dex-Lipstreatments reduced the expression of TNF-& alpha;, IL-1 & beta;, andIL-6 in DRG. Moreover, Dex-Lips could reduce inflammation in the cartilageand serum. Additionally, Dex-Lips repolarize synovial macrophagesto M2 phenotypes in miR-204/-211-deficient mice. In conclusion, Dex-Lipsinhibited the inflammatory response and alleviated the pain symptomsof OA by affecting the polarization of macrophages.