The detrimental effect of iron on OA chondrocytes: Importance of pro-inflammatory cytokines induced iron influx and oxidative stress.
The detrimental effect of iron on OA chondrocytes: Importance of pro-inflammatory cytokines induced iron influx and oxidative stress.
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DOI：
10.1111/jcmm.16581
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发表时间：
2021-06
影响因子：
5.3
通讯作者：
Cui X
中科院分区：
文献类型：
--
作者：
Jing X;Du T;Li T;Yang X;Wang G;Liu X;Jiang Z;Cui X
铁超载在老年人中很常见，与骨关节炎（OA）的发生发展密切相关，但OA发病和发展过程中铁稳态的调节机制及其对关节软骨细胞病理转变的影响尚不清楚。在本研究中，我们开发了一种体外方法来研究炎症环境下软骨细胞中铁稳态和铁过载介导的氧化应激的作用。我们发现促炎细胞因子可以通过上调铁内流转运蛋白TfR1和下调铁外流转运蛋白FPN来破坏软骨细胞铁稳态，从而导致软骨细胞铁过载。铁超载可促进软骨细胞分解代谢标志物MMP 3和MMP 13的表达。此外，我们发现氧化应激和线粒体功能障碍在铁超载诱导的软骨退行性变中发挥重要作用，使用铁螯合剂或抗氧化药物降低铁浓度可以抑制铁超载诱导的OA相关分解代谢标志物和线粒体功能障碍。我们的研究结果表明，促炎细胞因子可以破坏软骨细胞铁稳态并促进铁内流，铁过载诱导的氧化应激和线粒体功能障碍在铁过载诱导的软骨退变中起重要作用。
Iron overload is common in elderly people which is implicated in the disease progression of osteoarthritis (OA), however, how iron homeostasis is regulated during the onset and progression of OA and how it contributes to the pathological transition of articular chondrocytes remain unknown. In the present study, we developed an in vitro approach to investigate the roles of iron homeostasis and iron overload mediated oxidative stress in chondrocytes under an inflammatory environment. We found that pro‐inflammatory cytokines could disrupt chondrocytes iron homeostasis via upregulating iron influx transporter TfR1 and downregulating iron efflux transporter FPN, thus leading to chondrocytes iron overload. Iron overload would promote the expression of chondrocytes catabolic markers, MMP3 and MMP13 expression. In addition, we found that oxidative stress and mitochondrial dysfunction played important roles in iron overload‐induced cartilage degeneration, reducing iron concentration using iron chelator or antioxidant drugs could inhibit iron overload‐induced OA‐related catabolic markers and mitochondrial dysfunction. Our results suggest that pro‐inflammatory cytokines could disrupt chondrocytes iron homeostasis and promote iron influx, iron overload‐induced oxidative stress and mitochondrial dysfunction play important roles in iron overload‐induced cartilage degeneration.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
5.6
作者：
Zhang DL;Ghosh MC;Rouault TA
通讯作者：
Rouault TA
影响因子：
6.2
作者：
Kim, Beom-Jun;Ahn, Seong Hee;Kim, Ghi Su
通讯作者：
Kim, Ghi Su
影响因子：
5.6
作者：
Jing, Xingzhi;Du, Ting;Jiang, Zhensong
通讯作者：
Jiang, Zhensong
影响因子：
13.3
作者：
Lopez de Figueroa, Paloma;Lotz, Martin K.;Blanco, Francisco J.;Carames, Beatriz
通讯作者：
Carames, Beatriz