Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
J Cell Mol Med. 2024 Jun;28(11):e18476. doi: 10.1111/jcmm.18476.
Osteoarthritis (OA) is a complicated disease that involves apoptosis and mitophagy. MST1 is a pro-apoptotic factor. Hence, decreasing its expression plays an anti-apoptotic effect. This study aims to investigate the protective effect of MST1 inhibition on OA and the underlying processes. Immunofluorescence (IF) was used to detect MST1 expression in cartilage tissue. Western Blot, ELISA and IF were used to analyse the expression of inflammation, extracellular matrix (ECM) degradation, apoptosis and mitophagy-associated proteins. MST1 expression in chondrocytes was inhibited using siRNA and shRNA in vitro and in vivo. Haematoxylin-Eosin, Safranin O-Fast Green and alcian blue staining were used to evaluate the therapeutic effect of inhibiting MST1. This study discovered that the expression of MST1 was higher in OA patients. Inhibition of MST1 reduced inflammation, ECM degradation and apoptosis and enhanced mitophagy in vitro. MST1 inhibition slows OA progression in vivo. Inhibiting MST1 suppressed apoptosis, inflammation and ECM degradation via promoting Parkin-mediated mitophagy and the Nrf2-NF-κB axis. The results suggest that MST1 is a possible therapeutic target for the treatment of osteoarthritis as its inhibition delays the progression of OA through the Nrf2-NF-κB axis and mitophagy.
骨关节炎（OA）是一种涉及细胞凋亡和自噬的复杂疾病。MST1 是一种促凋亡因子。因此，降低其表达水平具有抗凋亡作用。本研究旨在探讨 MST1 抑制对 OA 及其潜在机制的保护作用。免疫荧光（IF）用于检测软骨组织中 MST1 的表达。Western Blot、ELISA 和 IF 用于分析炎症、细胞外基质（ECM）降解、凋亡和自噬相关蛋白的表达。体外和体内使用 siRNA 和 shRNA 抑制软骨细胞中的 MST1 表达。苏木精-伊红、番红 O-快绿和阿利新蓝染色用于评估抑制 MST1 的治疗效果。本研究发现，OA 患者中 MST1 的表达更高。抑制 MST1 可减少体外炎症、ECM 降解和凋亡，并增强自噬。体内抑制 MST1 可减缓 OA 进展。抑制 MST1 通过促进 Parkin 介导的自噬和 Nrf2-NF-κB 轴抑制凋亡、炎症和 ECM 降解。结果表明，MST1 可能是治疗骨关节炎的治疗靶点，其抑制作用通过 Nrf2-NF-κB 轴和自噬来延缓 OA 的进展。
