Yang Lin, Fan Changdong, Shu Taipengfei, Wang Shujun
Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, P.R. China.
Department of Emergency Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, P.R. China.
J Food Biochem. 2021 May 11:e13755. doi: 10.1111/jfbc.13755.
Forkhead box O3 (FOXO3) transcription factor is involved in chondral homeostasis of normal, aging and osteoarthritis (OA) cartilage. At present, we aimed to investigate whether FOXO3 is a target of punicalin to prevent IL-1β- and TNF-α-induced chondrocyte dysfunction in vitro and in vivo models. Cell and mouse models of chondrocyte dysfunction were established to determine the pharmacological value of hydrolyzable tannin, punicalin, which was extracted from the pomegranate. FOXO3 protein levels in the nucleus and cytoplasm were analysed using western blot. Safranine O staining was performed to evaluate the expansion of growth plate and chondrocyte differentiation in IL-1β- and TNF-α-treated mice. In IL-1β- and TNF-α-treated chondrocytes and mice, IL-1β and TNF-α evoked phosphorylation and nucleocytoplasmic shuttling of FOXO3, as well as reduced FOXO3 expression levels in the nucleus. However, punicalin treatment repressed FOXO3 phosphorylation and cytoplasmic transfer. Punicalin treatment improved IL-1β and TNF-α-induced growth inhibition and apoptosis of chondrocyte and the abnormal expansion of growth plate and hypertrophic zone. Moreover, punicalin could maintain the normal phenotype of chondrocyte via mediating multiple gene expression. Punicalin showed a beneficial effect on IL-1β- and TNF-α-stimulated chondrocytes and cartilaginous metabolic disorders via preserving the transcriptional activity of FOXO3. PRACTICAL APPLICATIONS: Our study presents a prospective adjuvant therapeutic drug, punicalin, to prevent inflammation-related cartilage injury and chondrocyte dysfunction.
叉头框O3（FOXO3）转录因子参与正常、衰老和骨关节炎（OA）软骨的软骨内稳态。目前，我们旨在研究FOXO3是否是石榴皮素的作用靶点，以在体外和体内模型中预防白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）诱导的软骨细胞功能障碍。建立软骨细胞功能障碍的细胞和小鼠模型，以确定从石榴中提取的可水解单宁石榴皮素的药理价值。使用蛋白质免疫印迹法分析细胞核和细胞质中FOXO3蛋白水平。进行番红O染色以评估IL-1β和TNF-α处理的小鼠生长板的扩展和软骨细胞分化。在IL-1β和TNF-α处理的软骨细胞和小鼠中，IL-1β和TNF-α引起FOXO3的磷酸化和核质穿梭，以及细胞核中FOXO3表达水平降低。然而，石榴皮素处理可抑制FOXO3磷酸化和细胞质转移。石榴皮素处理改善了IL-1β和TNF-α诱导的软骨细胞生长抑制和凋亡以及生长板和肥大带的异常扩展。此外，石榴皮素可通过介导多种基因表达维持软骨细胞的正常表型。石榴皮素通过保持FOXO3的转录活性，对IL-1β和TNF-α刺激的软骨细胞和软骨代谢紊乱显示出有益作用。实际应用：我们的研究提出了一种潜在的辅助治疗药物石榴皮素，以预防炎症相关的软骨损伤和软骨细胞功能障碍。
