Department of Orthopedics, Peking University First Hospital, Beijing 100034, China.
Department of Orthopedics, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830063, China.
Chin Med J (Engl). 2019 Nov 5;132(21):2581-2587. doi: 10.1097/CM9.0000000000000402.
Plant homeodomain finger protein 23 (PHF23) is a novel autophagy inhibitor gene that has been few studied with respect to orthopedics. This study was to investigate the expression of PHF23 in articular cartilage and synovial tissue, and analyze the relationship between PHF23 and chondrocyte autophagy in osteoarthritis (OA).
Immunohistochemical staining and western blot were applied to show the expression of PHF23 in cartilage of different outbridge grades and synovial tissue of patient with OA and healthy control. The normal human chondrocyte pre-treated with rapamycin or 3-methyladenine, treated with interleukin-1β (IL-1β). IL-1β induced expression level of PHF23 and autophagy-related proteins light chain 3B-I (LC3B-I), LC3B-II, and P62, were examined by Western blot. A PHF23 gene knock-down model was constructed with small interfering RNA. Western blot was performed to detect the efficiency of PHF23 and the impact of PHF23 knockout on IL-1β-induced expression of autophagy-related and apoptotic-related proteins in chondrocyte.
The expression of PHF23 was significantly increased in the high-grade cartilage and synovial tissue of patients with OA. The IL-1β-induced expression of PHF23 was gradually enhanced with time. The level of LC3B-II, P62 changed with time. After knockdown of PHF23, the level of autophagy-related proteins increased and apoptotic-related proteins decreased in IL-1β-induced OA-like chondrocytes.
The expression of PHF23 increased in human OA cartilage and synovium, and was induced by IL-1β through inflammatory stress. PHF23 can suppress autophagy of chondrocytes, and accelerate apoptosis.
植物同源结构域指蛋白 23（PHF23）是一种新型的自噬抑制剂基因，其在骨科领域的研究较少。本研究旨在探讨 PHF23 在关节软骨和滑膜组织中的表达，并分析 PHF23 与骨关节炎（OA）中软骨细胞自噬的关系。
采用免疫组化染色和 Western blot 检测不同桥接等级软骨和 OA 患者滑膜组织中 PHF23 的表达。用雷帕霉素或 3-甲基腺嘌呤预处理正常人软骨细胞，用白细胞介素-1β（IL-1β）处理。Western blot 检测 IL-1β诱导的 PHF23 及自噬相关蛋白 LC3B-I、LC3B-II 和 P62 的表达水平。用小干扰 RNA 构建 PHF23 基因敲低模型。Western blot 检测 PHF23 的敲低效率及其对 IL-1β诱导软骨细胞自噬相关和凋亡相关蛋白表达的影响。
PHF23 在 OA 患者高等级软骨和滑膜组织中的表达明显增加。IL-1β 诱导 PHF23 的表达随时间逐渐增强。LC3B-II、P62 的水平随时间变化。敲低 PHF23 后，IL-1β 诱导的 OA 样软骨细胞中自噬相关蛋白水平升高，凋亡相关蛋白水平降低。
PHF23 在人 OA 软骨和滑膜中的表达增加，且被 IL-1β 通过炎症应激诱导。PHF23 可抑制软骨细胞自噬，加速凋亡。
