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人脐带间充质干细胞脱细胞基质通过抑制STING-NF-κB通路减轻软骨细胞衰老。

Human umbilical cord mesenchymal stem cells decellular matrix alleviates chondrocyte senescence by inhibiting the STING-NF-κB pathway.

作者信息

Zhang Yuelong, Ren Xunshan, Zhuang Huangming, Li Huajie, Adam Miradj Siddick, Feng Rongling, Zhu Junming, Zhou Panghu

机构信息

Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

PLoS One. 2025 Jun 26;20(6):e0325704. doi: 10.1371/journal.pone.0325704. eCollection 2025.

DOI:10.1371/journal.pone.0325704
PMID:40569959
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12200692/
Abstract

Osteoarthritis (OA), characterized by synovial inflammation, articular cartilage degeneration, and structural changes of subchondral bone and periarticular tissues, represents a major unmet clinical challenge. Targeting senescent chondrocytes has emerged as a promising therapeutic strategy of OA. Human umbilgratical cord mesenchymal stem cells (hUCMSCs) have shown potential in OA treatment through paracrine mechanisms, but their clinical translation is limited by challenges in cell viability control and safety concerns. hUCMSCs decellular extracellular matrix (hUCMSCs-dECM) can target senescent chondrocytes to alleviate senescence in OA. Stimulator of interferon gene (STING) can promote chondrocyte senescence in OA through the activation of NF-κB signaling, and inhibition of STING may provide a novel approach for OA treatment. Here, we demonstrated that hUCMSCs-dECM attenuated chondrocyte senescence in vivo and in vitro by inhibiting the STING-NF-κB pathway, which would provide a novel approach for OA treatment.

摘要

骨关节炎(OA)以滑膜炎症、关节软骨退变以及软骨下骨和关节周围组织的结构改变为特征,是一个尚未得到充分解决的重大临床挑战。靶向衰老软骨细胞已成为一种有前景的OA治疗策略。人脐带间充质干细胞(hUCMSCs)已通过旁分泌机制在OA治疗中显示出潜力,但其临床转化受到细胞活力控制方面的挑战和安全性问题的限制。hUCMSCs去细胞外基质(hUCMSCs-dECM)可靶向衰老软骨细胞以减轻OA中的衰老。干扰素基因刺激物(STING)可通过激活NF-κB信号通路促进OA中的软骨细胞衰老,抑制STING可能为OA治疗提供一种新方法。在此,我们证明hUCMSCs-dECM通过抑制STING-NF-κB途径在体内和体外减轻软骨细胞衰老,这将为OA治疗提供一种新方法。

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本文引用的文献

1
MYL3 protects chondrocytes from senescence by inhibiting clathrin-mediated endocytosis and activating of Notch signaling.Myl3 通过抑制网格蛋白介导的内吞作用和激活 Notch 信号来保护软骨细胞免于衰老。
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Decellularized extracellular matrix in the treatment of spinal cord injury.
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NF-κB activation enhances STING signaling by altering microtubule-mediated STING trafficking.NF-κB 的激活通过改变微管介导的 STING 运输来增强 STING 信号。
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Sirt6 attenuates chondrocyte senescence and osteoarthritis progression.Sirt6 可减轻软骨细胞衰老和骨关节炎进展。
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Arthritis Res Ther. 2022 Nov 28;24(1):260. doi: 10.1186/s13075-022-02953-0.
8
Chondrogenic Potential of Human Umbilical Cord Mesenchymal Stem Cells Cultured with Exosome-Depleted Fetal Bovine Serum in an Osteoarthritis Mouse Model.在骨关节炎小鼠模型中,用耗尽外泌体的胎牛血清培养的人脐带间充质干细胞的成软骨潜力
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9
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Ann Transl Med. 2022 Sep;10(18):976. doi: 10.21037/atm-22-3912.
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