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机械负荷促进骨关节炎小鼠模型中内源性干细胞的迁移和软骨分化。

Mechanical Loading Promotes the Migration of Endogenous Stem Cells and Chondrogenic Differentiation in a Mouse Model of Osteoarthritis.

机构信息

Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin, 300070, China.

Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300070, China.

出版信息

Calcif Tissue Int. 2023 Mar;112(3):363-376. doi: 10.1007/s00223-022-01052-1. Epub 2022 Dec 25.

DOI:10.1007/s00223-022-01052-1
PMID:36566445
Abstract

Osteoarthritis (OA) is a major health problem, characterized by progressive cartilage degeneration. Previous works have shown that mechanical loading can alleviate OA symptoms by suppressing catabolic activities. This study evaluated whether mechanical loading can enhance anabolic activities by facilitating the recruitment of stem cells for chondrogenesis. We evaluated cartilage degradation in a mouse model of OA through histology with H&E and safranin O staining. We also evaluated the migration and chondrogenic ability of stem cells using in vitro assays, including immunohistochemistry, immunofluorescence, and Western blot analysis. The result showed that the OA mice that received mechanical loading exhibited resilience to cartilage damage. Compared to the OA group, mechanical loading promoted the expression of Piezo1 and the migration of stem cells was promoted via the SDF-1/CXCR4 axis. Also, the chondrogenic differentiation was enhanced by the upregulation of SOX9, a transcription factor important for chondrogenesis. Collectively, the results revealed that mechanical loading facilitated cartilage repair by promoting the migration and chondrogenic differentiation of endogenous stem cells. This study provided new insights into the loading-driven engagement of endogenous stem cells and the enhancement of anabolic responses for the treatment of OA.

摘要

骨关节炎(OA)是一个主要的健康问题,其特征是进行性软骨退化。先前的研究表明,机械加载可以通过抑制分解代谢活性来减轻 OA 症状。本研究评估了机械加载是否可以通过促进用于软骨形成的干细胞募集来增强合成代谢活性。我们通过 H&E 和番红 O 染色的组织学评估了 OA 小鼠模型中的软骨降解。我们还使用体外分析,包括免疫组织化学、免疫荧光和 Western blot 分析,评估了干细胞的迁移和软骨形成能力。结果表明,接受机械加载的 OA 小鼠对软骨损伤具有弹性。与 OA 组相比,机械加载促进了 Piezo1 的表达,并通过 SDF-1/CXCR4 轴促进了干细胞的迁移。此外,转录因子 SOX9 的上调增强了软骨分化,SOX9 对于软骨形成很重要。总的来说,这些结果表明,机械加载通过促进内源性干细胞的迁移和软骨分化来促进软骨修复。本研究为负载驱动内源性干细胞参与和增强 OA 治疗的合成代谢反应提供了新的见解。

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本文引用的文献

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Calcif Tissue Int. 2022 Aug;111(2):171-184. doi: 10.1007/s00223-022-00976-y. Epub 2022 Apr 16.
2
Piezo Channels: Awesome Mechanosensitive Structures in Cellular Mechanotransduction and Their Role in Bone.压电通道:细胞机械转导中的强大机械敏感结构及其在骨骼中的作用。
Int J Mol Sci. 2021 Jun 16;22(12):6429. doi: 10.3390/ijms22126429.
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Advancements in tissue engineering for articular cartilage regeneration.用于关节软骨再生的组织工程学进展。
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