白细胞介素-10通过调节STAT3信号通路减轻与血友病关节病相关的软骨细胞下垂。

IF 3 2区 医学 Q2 HEMATOLOGY
Haemophilia Pub Date : 2025-08-25 DOI:10.1111/hae.70093
Fudong Luo, Yi Hu, Yi Wang, Dasheng Luo, Tao Chen, Defu Yu
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引用次数: 0

摘要

血友病(HA)的特点是复发性关节内出血导致软骨变性。上睑下垂在这一过程中起关键作用。虽然已知IL-10可抑制细胞凋亡,但其对铁下垂的影响仍未被探索。目的:探讨IL-10通过STAT3信号通路在嗜同性关节病软骨细胞凋亡中的作用。方法:采用透射电镜(TEM)和免疫印迹(Western blot)对HA和OA患者软骨标本进行铁沉积和IL-10检测。用FAC(铁超载)、Erastin(铁下垂诱导剂)和IL-10±STAT3抑制剂(AG-490)处理ATDC5软骨细胞。细胞活力测定、免疫印迹、活性氧检测和免疫荧光染色。测定细胞活力、ROS和通路蛋白。结果:与OA对照组相比,HA软骨细胞表现出线粒体铁沉积升高和IL-10降低。IL-10抑制铁下垂的效果与fe -1相当,机制依赖于STAT3的激活。结论:IL-10主要通过STAT3信号传导抑制HA软骨细胞的铁下垂,为其治疗HA的潜力提供了理论支持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Interleukin-10 Mitigates Chondrocyte Ferroptosis Associated With Haemophilic Arthropathy via Modulation of the STAT3 Signalling Pathway

Interleukin-10 Mitigates Chondrocyte Ferroptosis Associated With Haemophilic Arthropathy via Modulation of the STAT3 Signalling Pathway

Introduction

Haemophilic arthropathy (HA) is characterized by recurrent intra-articular bleeding leading to cartilage degeneration. Ferroptosis plays a critical role in this process. While IL-10 is known to inhibit apoptosis, its effect on ferroptosis remains unexplored.

Aim

To investigate IL-10's role in chondrocyte ferroptosis in homophilic arthropathy via STAT3 signalling.

Methods

Cartilage samples from HA and OA patients were analyzed by TEM and Western blot for iron deposition and IL-10. ATDC5 chondrocytes were treated with FAC (iron overload), Erastin (ferroptosis inducer) and IL-10±STAT3 inhibitor (AG-490). Cell viability assays, Western blotting, reactive oxygen species detection and immunofluorescent staining were performed. Viability, ROS and pathway proteins were assessed.

Results

HA chondrocytes exhibited elevated mitochondrial iron deposition and reduced IL-10 versus OA controls. IL-10 suppressed ferroptosis with efficacy comparable to Fer-1, mechanistically dependent on STAT3 activation.

Conclusion

IL-10 suppresses ferroptosis in HA chondrocytes primarily via STAT3 signalling, providing theoretical support for its therapeutic potential for HA.

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来源期刊
Haemophilia
Haemophilia 医学-血液学
CiteScore
6.50
自引率
28.20%
发文量
226
审稿时长
3-6 weeks
期刊介绍: Haemophilia is an international journal dedicated to the exchange of information regarding the comprehensive care of haemophilia. The Journal contains review articles, original scientific papers and case reports related to haemophilia care, with frequent supplements. Subjects covered include: clotting factor deficiencies, both inherited and acquired: haemophilia A, B, von Willebrand''s disease, deficiencies of factor V, VII, X and XI replacement therapy for clotting factor deficiencies component therapy in the developing world transfusion transmitted disease haemophilia care and paediatrics, orthopaedics, gynaecology and obstetrics nursing laboratory diagnosis carrier detection psycho-social concerns economic issues audit inherited platelet disorders.
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