Trauma Center, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou 213003, China.
Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Aging (Albany NY). 2023 Jun 23;15(12):5775-5797. doi: 10.18632/aging.204837.
Chondrocyte degeneration and classically activated macrophage (AM)-related inflammation play critical roles in osteoarthritis (OA). Here, we explored the effects of astaxanthin and Rspo2 on OA and . We observed that the Rspo2 gene was markedly elevated in synovial tissues of OA patients compared with healthy controls. In 2D cultures, Rspo2 and inflammatory factors were enhanced in AMs compared with nonactivated macrophages (NMs), and the protein expression levels of Rspo2, β-catenin, and inflammatory factors were increased, and anabolic markers were reduced in osteoarthritic chondrocytes (OACs) compared to normal chondrocytes (NCs). Astaxanthin reversed these changes in AMs and OACs. Furthermore, Rspo2 shRNA significantly abolished inflammatory factors and elevated anabolic markers in OACs. In NCs cocultured with AM, and in OACs cocultured with AMs or NMs, astaxanthin reversed these changes in these coculture systems and promoted secretion of Rspo2, β-catenin and inflammatory factors and suppressed anabolic markers compared to NCs or OACs cultured alone. In AMs, coculture with NCs resulted in a slight elevation of Rspo2 and AM-related genes, but not protein expression, compared to culture alone, but when cocultured with OACs, these inflammatory mediators were significantly enhanced at both the gene and protein levels. Astaxanthin reversed these changes in all the groups. , we observed a deterioration in cartilage quality after intra-articular injection of Rspo2 associated with medial meniscus (DMM)-induced instability in the OA group, and astaxanthin was protective in these groups. Our results collectively revealed that astaxanthin attenuated the process of OA by abolishing Rspo2 both and .
软骨细胞退变和经典激活的巨噬细胞（AM）相关炎症在骨关节炎（OA）中起关键作用。在这里，我们探讨了虾青素和 Rspo2 对 OA 的影响。我们观察到，与健康对照组相比，OA 患者的滑膜组织中 Rspo2 基因明显升高。在 2D 培养中，与未激活的巨噬细胞（NMs）相比，Rspo2 和炎症因子在 AMs 中增强，并且 Rspo2、β-连环蛋白和炎症因子的蛋白表达水平增加，而在 OA 软骨细胞（OACs）中，合成代谢标志物与正常软骨细胞（NCs）相比降低。虾青素逆转了 AM 和 OAC 中的这些变化。此外，Rspo2 shRNA 显著消除了 OAC 中的炎症因子并升高了合成代谢标志物。在与 AM 共培养的 NCs 中，以及在与 AM 或 NMs 共培养的 OACs 中，与单独培养的 NCs 或 OACs 相比，虾青素逆转了这些共培养系统中的变化，并促进了 Rspo2、β-连环蛋白和炎症因子的分泌，并抑制了合成代谢标志物的分泌。在 AM 中，与单独培养相比，与 NCs 共培养仅导致 Rspo2 和 AM 相关基因轻度升高，但蛋白表达没有升高，但与 OAC 共培养时，这些炎症介质的基因和蛋白水平均显著升高。虾青素逆转了所有组中的这些变化。此外，我们观察到在 OA 组中，与内侧半月板（DMM）诱导的不稳定相关的关节内注射 Rspo2 后，软骨质量恶化，虾青素在这些组中具有保护作用。我们的研究结果共同揭示，虾青素通过在体内和体外均消除 Rspo2 来减轻 OA 的发生过程。
