Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430072, China.
Int J Mol Sci. 2023 Mar 6;24(5):5056. doi: 10.3390/ijms24055056.
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.
衰老细胞的积累是骨关节炎（OA）的突出风险因素，通过衰老相关分泌表型（SASP）加速 OA 的进展。最近的研究强调了 OA 中存在衰老的滑膜细胞以及去除衰老滑膜细胞的治疗效果。由于其独特的清除 ROS 的能力，氧化铈纳米颗粒（CeNP）在多种与年龄相关的疾病中表现出治疗效果。然而，CeNP 在 OA 中的作用尚不清楚。我们的结果表明，CeNP 通过清除 ROS 抑制了多代和过氧化氢处理的滑膜细胞中衰老和 SASP 生物标志物的表达。在体内，CeNP 关节内注射后，滑膜组织中的 ROS 浓度明显受到抑制。同样，免疫组织化学分析显示 CeNP 降低了衰老和 SASP 生物标志物的表达。机制研究表明，CeNP 使衰老的滑膜细胞中的 NFκB 通路失活。最后，番红 O-快绿染色显示 CeNP 处理组的关节软骨破坏程度比 OA 组更轻。总的来说，我们的研究表明，CeNP 通过清除 ROS 和使 NFκB 信号通路失活来减轻衰老并保护软骨免受退化。这项研究在 OA 领域具有潜在的重要意义，因为它为 OA 的治疗提供了一种新策略。
