s -丙炔半胱氨酸通过抑制JAK/STAT信号调节巨噬细胞极化,减轻颞下颌关节骨性关节炎。

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Wenyi Cai, Antong Wu, Zhongxiao Lin, Wei Cao, Janak L Pathak, Richard T Jaspers, Rui Li, Xin Li, Kaihan Zheng, Yufu Lin, Na Zhou, Xin Zhang, Yizhun Zhu, Qingbin Zhang
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引用次数: 0

摘要

背景:颞下颌关节骨性关节炎(TMJ-OA)是一种以软骨退化和滑膜炎症为特征的疾病,目前有效的治疗方法有限。滑膜巨噬细胞极化是TMJ-OA进展的关键,使其成为一个有前景的治疗方面。本研究探讨了内源性H2S供体s -丙炔基半胱氨酸(SPRC)对巨噬细胞极化的影响及其缓解TMJ-OA的治疗潜力。方法:采用mia诱导的TMJ-OA大鼠模型和lps刺激的RAW264.7巨噬细胞,在体内和体外评价SPRC的作用。通过显微ct和组织学方法分析TMJ骨和软骨,通过RT-qPCR、western blot和免疫荧光检测巨噬细胞极化标志物的表达。在巨噬细胞上进行RNA测序,并使用JAK2特异性抑制剂AG490验证JAK2/STAT3信号通路。通过观察ECM的合成和降解,探讨SPRC对大鼠原代髁突软骨细胞的直接影响。共培养实验进一步评估了巨噬细胞-软骨细胞的相互作用。结果:SPRC可显著改善TMJ-OA大鼠模型的骨体积和软骨结构,显著减轻其软骨和骨损伤。SPRC减少促炎M1巨噬细胞浸润,增强抗炎M2巨噬细胞极化。SPRC有效抑制JAK2/STAT3,导致炎症标志物减少,包括TNF-α、IL-6和iNOS。共培养实验显示,sprc处理的巨噬细胞条件培养基改善了软骨细胞代谢活性,恢复了ECM的完整性。结论:sprc调控的巨噬细胞极化通过下调JAK/STAT来缓解TMJ-OA,从而减轻滑膜炎症和软骨退化。这些发现将SPRC定位为TMJ-OA的有希望的治疗候选药物,并为针对巨噬细胞极化和滑膜-软骨串扰的新策略提供了见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
S-propargyl-cysteine attenuates temporomandibular joint osteoarthritis by regulating macrophage polarization via Inhibition of JAK/STAT signaling.

Background: Temporomandibular joint osteoarthritis (TMJ-OA) is a disease characterized by cartilage degradation and synovial inflammation, with limited effective treatment currently. Synovial macrophage polarization is pivotal in TMJ-OA progression, making it a promising therapeutic aspect. This study investigated the effects of S-propargyl-cysteine (SPRC), an endogenous H2S donor, on macrophage polarization and its therapeutic potential in alleviating TMJ-OA.

Methods: A MIA-induced TMJ-OA rat model and LPS-stimulated RAW264.7 macrophages were employed to evaluate the effects of SPRC in vivo and in vitro. TMJ bone and cartilage were analyzed via micro-CT and histological methods, while macrophage polarization markers expression were assessed via RT-qPCR, western blot, and immunofluorescence. RNA sequencing was performed on macrophages, and the JAK2/STAT3 signaling pathway was validated using the JAK2-specific inhibitor AG490. The direct effects of SPRC on rat primary condylar chondrocytes were examined by evaluating ECM synthesis and degradation. Co-culture experiments further assessed macrophage-chondrocyte interactions.

Results: SPRC significantly alleviated cartilage and bone damage in the TMJ-OA rat model, as demonstrated by improved bone volume and cartilage structure. SPRC reduced pro-inflammatory M1 macrophage infiltration and enhanced anti-inflammatory M2 macrophage polarization. SPRC effectively inhibited the JAK2/STAT3, leading to reduction of inflammatory markers, including TNF-α, IL-6, and iNOS. Co-culture experiments revealed that SPRC-treated macrophage-conditioned medium improved chondrocyte metabolic activity and restored ECM integrity.

Conclusions: SPRC-modulated macrophage polarization alleviates TMJ-OA via JAK/STAT downregulation, thereby reducing synovial inflammation and cartilage degradation. These findings position SPRC as a promising therapeutic candidate for TMJ-OA and provide insights into novel strategies targeting macrophage polarization and synovium-cartilage crosstalk.

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来源期刊
Molecular Medicine
Molecular Medicine 医学-生化与分子生物学
CiteScore
8.60
自引率
0.00%
发文量
137
审稿时长
1 months
期刊介绍: Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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