铁凋亡与几种疾病有关,包括铁过载诱导的骨关节炎(IOOA),以氧化应激为标志,铁失衡,和脂质过氧化。鉴于罗格列酮(RSG)抑制脂质过氧化和铁凋亡的能力,本研究旨在评估其治疗IOOA的潜力.我们的体外结果表明,RSG靶向酰基辅酶A合成酶长链家族成员4,以减轻白细胞介素-1β和柠檬酸铁铵诱导的损伤,包括细胞凋亡,衰老,炎症反应,细胞外基质降解,和铁中毒。RSG降低细胞内铁含量,减轻氧化应激和脂质过氧化,减轻对膜结合细胞器的损害,和增强葡萄糖转运。此外,用RSG预处理赋予软骨细胞抗铁性。在体内,RSG缓解软骨降解,炎症反应,和患有IOOA的小鼠的铁性凋亡。总之,RSG通过抑制脂质过氧化和恢复铁稳态表现出软骨保护和抗铁作用。强调其治疗IOOA的潜力。
Ferroptosis is implicated in several diseases, including iron overload-induced osteoarthritis (IOOA), which is marked by oxidative stress, iron imbalance, and lipid peroxidation. Given rosiglitazone\'s (RSG) ability to inhibit lipid peroxidation and ferroptosis, this study aims to assess its therapeutic potential for treating IOOA. Our in vitro results show that RSG targets acyl-CoA synthetase long-chain family member 4 to mitigate impairments induced by interleukin-1 beta and ferric ammonium citrate, including cell apoptosis, senescence, inflammatory responses, extracellular matrix degradation, and ferroptosis. RSG reduced intracellular iron content, alleviated oxidative stress and lipid peroxidation, mitigated damage to membrane-bound organelles, and enhanced glucose transport. Additionally, pre-treatment with RSG imparted anti-ferroptotic properties to chondrocytes. In vivo, RSG alleviated cartilage degradation, inflammatory responses, and ferroptosis in mice with IOOA. In conclusion, RSG exhibits chondroprotective and anti-ferroptotic effects by suppressing lipid peroxidation and restoring iron homeostasis, highlighting its potential for treating IOOA.