骨性关节炎（OA）是临床上最常见的致残性关节疾病。大量研究提示异常的全身或局部的铁过载和OA相关。申请人前期的研究发现铁过载是OA进展的重要危险因素，炎症因子可促进软骨细胞铁代谢调节蛋白（IRP1）的表达升高和铁离子的内流。我们猜测IRP1介导的软骨细胞铁过载参与OA的病理进展，细胞内过量铁通过破坏线粒体的功能，抑制线粒体自噬导致软骨细胞的死亡。本课题拟在前期研究的基础上，运用基因表达调控、组织学及分子生物学等技术，从动物、细胞和分子整体水平系统研究OA软骨细胞铁代谢的改变，阐明铁过载对软骨细胞炎症状态下凋亡、分化、线粒体自噬等的影响，深入研究软骨细胞炎性环境下IRP1对铁代谢的调控及其对线粒体功能和自噬的影响。目的在于揭示IRP1介导的软骨细胞铁过载对线粒体自噬的调控及其对OA病理进程的影响，为早期预防和后期治疗OA提供理论基础和实验依据。

Osteoarthritis (OA) is the most common cause of disabling arthritis. Many studies have indicated that systemic or local iron overload is associated with OA, but its underlying mechanism is still unclear. Our previous studies have shown that iron overload is an important risk factor for OA progress. Inflammatory cytokines could promote the expression of iron regulatory protein (IRP1) and influx of iron ions in chondrocytes. We speculate that IRP1-mediated chondrocyte iron overload is involved in the pathological progression of OA, excess intracellular iron could disrupt mitochondrial function, suppress mitochondrial autophagy and lead to chondrocytes apoptosis. In this study, gene expression regulation, histology and molecular biology techniques from animal, cell and molecular level will be used to study the change of iron metabolism in OA chondrocyte, explore the effect of iron overload on chondrocyte apoptosis, differentiation and mitochondrial autophagy, this study will further investigate the effect of IRP1/TfR1 pathway on iron metabolism regulation, mitochondrial function and mitochondrial autophagy. We aim to reveal the effect of IRP1 on mitochondrial autophagy regulation and the pathological process of OA. This study will provide a new experimental and theoretical basis for early prevention and further treatment of OA.