Ceria Nanoparticles Alleviated Osteoarthritis through Attenuating Senescence and Senescence-Associated Secretory Phenotype in Synoviocytes
Xunshan Ren, Huangming Zhuang, Fuze Jiang, Yuelong Zhang, Panghu Zhou
Abstract
Accumulation of senescent cells is the prominent risk factor for osteoarthritis (OA), accelerating the progression of OA through a senescence-associated secretory phenotype (SASP). Recent studies emphasized the existence of senescent synoviocytes in OA and the therapeutic effect of removing senescent synoviocytes. Ceria nanoparticles (CeNP) have exhibited therapeutic effects in multiple age-related diseases due to their unique capability of ROS scavenging. However, the role of CeNP in OA remains unknown. Our results revealed that CeNP could inhibit the expression of senescence and SASP biomarkers in multiple passaged and hydrogen-peroxide-treated synoviocytes by removing ROS. In vivo, the concentration of ROS in the synovial tissue was remarkably suppressed after the intra-articular injection of CeNP. Likewise, CeNP reduced the expression of senescence and SASP biomarkers as determined by immunohistochemistry analysis. The mechanistic study showed that CeNP inactivated the NFκB pathway in senescent synoviocytes. Finally, safranin O-fast green staining showed milder destruction of articular cartilage in the CeNP-treated group compared with the OA group. Overall, our study suggested that CeNP attenuated senescence and protected cartilage from degeneration via scavenging ROS and inactivating the NFκB signaling pathway. This study has potentially significant implications in the field of OA as it provides a novel strategy for OA treatment.