Rps6ka2 enhances iMSC chondrogenic differentiation to attenuate knee osteoarthritis through articular cartilage regeneration in mice

Articular cartilage (AC) is most susceptible to degeneration in knee osteoarthritis (OA); however, the existing treatments for OA do not target the core link of the pathogenesis-"decreased tissue cell function activity and extracellular matrix (ECM) metabolic disorders” for effective intervention. iMSC hold lower heterogeneity and great promise in biological research and clinical applications. Rps6ka2 may play an important role in the iMSC to treat OA. In this study, the CRISPR/Cas9 gene editing Rps6ka2−/− iMSC were obtained. Effect of Rps6ka2 on iMSC proliferation and chondrogenic differentiation was evaluated in vitro. An OA model was constructed in mice by surgical destabilization of medial meniscus (DMM). The Rps6ka2−/− iMSC and iMSC were injected into the articular cavity twice-weekly for 8 weeks. In vitro experiments showed that Rps6ka2 could promote iMSC proliferation and chondrogenic differentiation. In vivo results further confirmed that Rps6ka2 could improve iMSC viability to promote ECM production to attenuate OA in mice. •Both iMSC and Rps6ka2−/− iMSC could be differentiated into chondrocytes adipocytes and osteoblasts.•Rps6ka2−/− iMSC-chondrogenic pellets possessed down-regulated differentiation mRNAs compared to iMSC-chondrogenic pellets.•Rps6ka2 could promote iMSC proliferation and chondrogenic differentiation in vitro.•Rps6ka2 could improve iMSC viability to promote ECM production to attenuate OA.•Rps6ka2 has the potential to enhance iMSC chondrogenic differentiation to attenuate OA through AC regeneration.