Ceria Nanoparticles Reduce the Impact of Senescent Cells in Osteoarthritic Joints

The lingering senescent cells characteristic of old tissues contribute to the pathology of osteoathritis via their constant disruptive inflammatory signaling, the senescence-associated secretory phenotype (SASP). Researchers recently reported that the use of antioxidant ceria nanoparticles can reduce the SASP in joint tissue, acting on important regulators that control the generation of the SASP. In this context, it is worth noting that both human and animal evidence suggests that local clearance of senescent cells or local inhibition of SASP in the joint is not sufficient to turn back osteoathritis. Senescent cells elsewhere in the body may be more distant, but there are a lot more of them, and they all generate pro-inflammatory signaling that impacts the joint environment.

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 reactive oxygen species (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.

Link: https://doi.org/10.3390/ijms24055056

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