Novel strategy of senescence elimination via toxicity-exempted kinome perturbations by nanoliposome-based thermosensitive hydrogel for osteoarthritis therapy

Abstract Cellular senescence and the senescence-associated secretory phenotype (SASP) have been implicated in osteoarthritis (OA). This study aims to determine whether multi-kinase inhibitor YKL-05-099 (Y099) has potential elimination OA therapy delivering Y099 by nanoliposmal hydrogel improves performance of kinase inhibitor. inhibited IL-1β-induced inflammation catabolism promoted anabolism chondrocytes. To attenuate inhibition cell viability, nanoliposomal Y099-loaded thermosensitive (Y099-Lip-Gel) was developed for sustained release toxicity exemption. Notably, Y099-Lip-Gel exhibited a pronounced effect on promoting suppressing without causing chondrocyte viability. Moreover, remarkably increased master regulator Sox9 expression. After four intra-articular injections murine model, histological lesions cartilage were attenuated with subchondral bone loss osteoclast formation inhibited. Transcriptomic analysis experimental validations revealed that suppressed cellular inhibiting expression inducers SASP factors. Furthermore, phosphoproteomic showed exerted significant influence kinome phosphorylation, MAPK NF-κB signaling activations. The protective effects also validated cultured human explants. In conclusion, considerable therapy. Nanoliposome-based system strength reducing inhibition-induced cytotoxicity, enhancing tolerance perturbation, improving protein inhibitors. Senescence via toxicity-exempted perturbations achieved advanced nanotechnology is promising strategy OA. Graphical