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白细胞介素-10 通过 JAK/Stat3 通路促进肌腱来源干细胞的增殖和迁移,并抑制其在体外的肌腱分化。

Interleukin‑10 promotes proliferation and migration, and inhibits tendon differentiation via the JAK/Stat3 pathway in tendon‑derived stem cells in vitro.

机构信息

Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

The Third Clinical College of Guangzhou Medical University, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Mol Med Rep. 2018 Dec;18(6):5044-5052. doi: 10.3892/mmr.2018.9547. Epub 2018 Oct 10.

DOI:10.3892/mmr.2018.9547
PMID:30320384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6236255/
Abstract

Tendon repair follows a slow course of early inflammatory, proliferative and remodeling phases, which commonly results in the failure and loss of normal biomechanical properties. Previous studies have demonstrated that tendon‑derived stem cells (TDSCs) are vital healing cells and that mRNA expression of anti‑inflammatory cytokine interleukin (IL)‑10 is significantly upregulated at the late inflammatory phase. To explore how IL‑10 may impact tendon healing, the present study investigated the in vitro effects of IL‑10 on TDSCs isolated from rat Achilles tendons. Cellular activities of TDSCs and the expression levels of tendon cell markers were measured treatment with IL‑10 and subsequent performance of wound healing assays, reverse transcription‑quantitative polymerase chain reaction and western blot analyses. The results demonstrated that IL‑10 treatment markedly increased the proliferative capacity of TDSCs. In addition, IL‑10 significantly enhanced cell migration when compared with the control cells. Furthermore, IL‑10 treatment significantly activated the JAK/Stat3 signaling pathway and inhibited the protein expression of tendon cell markers, including scleraxis and tenomodulin. Notably, IL‑10 treatment also reduced the gene expression levels of type 1 collagen, type 3 collagen, lumican and fibromodulin in TDSCs. These findings indicated that IL‑10 enhanced cell proliferation and migration, and inhibited tenogenic differentiation in TDSCs in vitro. Reducing the negative effects whilst enhancing the positive effects of IL‑10 may be a potential therapeutic target in tendon repair.

摘要

肌腱修复遵循早期炎症、增殖和重塑阶段的缓慢过程,通常导致正常生物力学特性的丧失和失败。先前的研究表明,肌腱来源的干细胞(TDSCs)是重要的愈合细胞,炎症晚期 IL-10 抗炎细胞因子的 mRNA 表达显著上调。为了探索 IL-10 如何影响肌腱愈合,本研究探讨了 IL-10 对从小鼠跟腱分离的 TDSCs 的体外作用。通过 IL-10 处理和随后进行的伤口愈合测定、逆转录-定量聚合酶链反应和 Western blot 分析,测量 TDSCs 的细胞活性和肌腱细胞标志物的表达水平。结果表明,IL-10 处理显著增加了 TDSCs 的增殖能力。此外,与对照细胞相比,IL-10 显著增强了细胞迁移。此外,IL-10 处理显著激活了 JAK/Stat3 信号通路,并抑制了肌腱细胞标志物,包括 Scleraxis 和 Tenomodulin 的蛋白表达。值得注意的是,IL-10 处理还降低了 TDSCs 中 I 型胶原、III 型胶原、Lumican 和 Fibromodulin 的基因表达水平。这些发现表明,IL-10 在体外增强了 TDSCs 的细胞增殖和迁移,并抑制了肌腱生成分化。减少 IL-10 的负面影响并增强其积极作用可能是肌腱修复的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/5d26c62cb282/MMR-18-06-5044-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/cfd70d982cdb/MMR-18-06-5044-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/aacd153c120f/MMR-18-06-5044-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/9153a030fa26/MMR-18-06-5044-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/0f87e0cd43c4/MMR-18-06-5044-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/5d26c62cb282/MMR-18-06-5044-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/cfd70d982cdb/MMR-18-06-5044-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/aacd153c120f/MMR-18-06-5044-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/9153a030fa26/MMR-18-06-5044-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/0f87e0cd43c4/MMR-18-06-5044-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6ee/6236255/5d26c62cb282/MMR-18-06-5044-g04.jpg

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