Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair.

IF 3.3 4区 医学 Q3 IMMUNOLOGY Autoimmunity Pub Date : 2024-12-01 Epub Date: 2024-07-01 DOI:10.1080/08916934.2024.2364686
Wenjuan Xu, Yuanyuan Zhang, Lijuan Li, Liyan Pan, Li Lu, Shenshen Zhi, Wei Li
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Abstract

Background: Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA.

Objective: This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms.

Methods: An injury cell model was established by treating chondrocytes with IL-1β. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo.

Results: Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2.

Conclusion: Osteocyte-derived exosomal DLX2 alleviated IL-1β-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.

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骨细胞源性外泌体调节 DLX2/wnt 通路,通过介导软骨修复缓解骨关节炎。
背景:软骨细胞的活力、凋亡和迁移与骨关节炎(OA)关节软骨损伤密切相关。外泌体被认为是治疗 OA 的潜在药物:本研究旨在探讨从骨细胞中提取的外泌体在 OA 中的作用,特别是其对软骨修复的影响和分子机制:方法:用 IL-1β 处理软骨细胞,建立损伤细胞模型。方法:用 IL-1β 处理软骨细胞,建立损伤细胞模型,使用细胞计数试剂盒-8、流式细胞术、划痕试验和 Western Blot 评估软骨修复情况。使用定量实时 PCR、生物信息分析和 Western 印迹分析了分子机制。建立了OA小鼠模型,以探索外泌体DLX2在体内的作用:结果:骨细胞释放的外泌体促进了细胞活力和迁移,抑制了细胞凋亡和细胞外基质(ECM)沉积。此外,外泌体可上调 DLX2 的表达,敲除 DLX2 可激活 Wnt 通路。此外,外泌体通过传递 DLX2 减轻了小鼠的 OA:结论:骨细胞衍生的外泌体DLX2可缓解IL-1β诱导的软骨修复,并使Wnt通路失活,从而缓解OA进展。研究结果表明,骨细胞衍生的外泌体有望成为治疗OA的一种方法。
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来源期刊
Autoimmunity
Autoimmunity 医学-免疫学
CiteScore
5.70
自引率
8.60%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.
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