钙螯合剂 BAPTA-AM 可防止铁过载引起的软骨细胞线粒体功能障碍和软骨退化。,International Journal of Molecular Medicine

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钙螯合剂 BAPTA-AM 可防止铁过载引起的软骨细胞线粒体功能障碍和软骨退化。
International Journal of Molecular Medicine ( IF 5.7 ) Pub Date : 2021-09-01 , DOI: 10.3892/ijmm.2021.5029
Xingzhi Jing ₁ , Qiang Wang ₂ , Ting Du ₃ , Weimin Zhang ₁ , Xiaoyang Liu ₁ , Qiang Liu ₃ , Tao Li ₁ , Guodong Wang ₁ , Feifei Chen ₁ , Xingang Cui ₁

Affiliation

骨关节炎（OA）是一种以软骨退化为特征的常见关节疾病。关节中的铁沉积在 OA 的发病过程中很常见，最近的研究表明，铁超负荷是 OA 进展的重要因素。据报道，钙螯合剂通过调节转铁蛋白受体蛋白 1 内化来抑制铁内流，它们已被确定为治疗铁过载引起的疾病的潜在方法。本研究的目的是研究钙螯合剂对铁过载诱导的 OA 进展的影响。用不同浓度的柠檬酸铁铵 (FAC) 处理原代软骨细胞以在体外模拟铁过载，然后与钙螯合剂 BAPTA 乙酰氧基甲酯 (BAPTA-AM) 共同处理。随后，使用商业试剂盒检测细胞内铁水平、细胞活力、活性氧 (ROS) 水平、线粒体功能和形态变化以及 MMP 水平。结果表明，FAC 处理显着促进了软骨细胞凋亡和 MMPs 的表达，而这些作用通过与 BAPTA-AM 的共同处理而被逆转。此外，BAPTA-AM 抑制铁流入软骨细胞并抑制铁过载诱导的 ROS 产生和线粒体功能障碍。这些结果表明，钙螯合剂可能对治疗铁代谢相关疾病和铁过载诱导的 OA 进展具有价值。

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Calcium chelator BAPTA‑AM protects against iron overload‑induced chondrocyte mitochondrial dysfunction and cartilage degeneration.

Osteoarthritis (OA) is a common joint disease that is characterized by cartilage degradation. Iron deposition in the joints is common during the pathogenic progression of OA and recent studies have indicated that iron overload is an important contributor to OA progression. Calcium chelators have been reported to inhibit iron influx via modulating transferrin receptor protein 1 internalization, and they have been identified as a potential approach to the treatment of iron overload‑induced diseases. The aim of the present study was to investigate the effect of calcium chelators on the progression of iron overload‑induced OA. Primary chondrocytes were treated with various concentrations of ferric ammonium citrate (FAC) to mimic iron overload in vitro, followed by co‑treatment with the calcium chelator BAPTA acetoxymethyl ester (BAPTA‑AM). Subsequently, intracellular iron levels, cell viability, reactive oxygen species (ROS) levels, mitochondrial function and morphological changes, as well as MMP levels, were detected using commercial kits. It was demonstrated that FAC treatment significantly promoted chondrocyte apoptosis and the expression of MMPs, and these effects were reversed by co‑treatment with BAPTA‑AM. Moreover, BAPTA‑AM suppressed iron influx into chondrocytes and inhibited iron overload‑induced ROS production and mitochondrial dysfunction. These results indicated that calcium chelators may be of value in the treatment of iron metabolism‑related diseases and iron overload‑induced OA progression.

更新日期：2021-09-01

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