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MicroRNA-21 通过靶向软骨细胞中的 GDF-5 来控制骨关节炎的发展。

MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes.

机构信息

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Exp Mol Med. 2014 Feb 28;46(2):e79. doi: 10.1038/emm.2013.152.

Abstract

Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. Altered chondrogenesis is the most important pathophysiological process involved in the development of osteoarthritis. However, the molecular mechanism underlying the regulation of chondrogenesis in patients with osteoarthritis requires further elucidation, particularly with respect to the role of microRNAs. MiR-21 expression in cartilage specimens was examined in 10 patients with knee osteoarthritis and 10 traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated in a chondrocyte cell line. The effect of miR-21 on the expression of growth differentiation factor 5 (GDF-5) was further assessed by luciferase reporter assay and western blot. We found that endogenous miR-21 is upregulated in osteoarthritis patients, and overexpression of miR-21 could attenuate the process of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR-21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an important role in the pathogenesis of osteoarthritis and is a potential therapeutic target.

摘要

骨关节炎是老年人功能恶化的常见原因,也是老龄化人口的巨大负担。软骨生成的改变是骨关节炎发展中涉及的最重要的病理生理过程。然而,骨关节炎患者软骨生成调节的分子机制尚需进一步阐明,特别是在 microRNA 的作用方面。在 10 例膝关节骨关节炎患者和 10 例创伤性截肢患者的软骨标本中检测了 miR-21 的表达。还在软骨细胞系中研究了 miR-21 对软骨生成的影响。通过荧光素酶报告基因检测和 Western blot 进一步评估了 miR-21 对生长分化因子 5 (GDF-5) 表达的影响。我们发现内源性 miR-21 在骨关节炎患者中上调,miR-21 的过表达可减弱软骨生成过程。此外,我们确定 GDF-5 是 miR-21 在调控软骨生成过程中的直接靶标。我们的数据表明,miR-21 在骨关节炎的发病机制中起重要作用,是一个有潜力的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ee/3944443/bde859bb955b/emm2013152f1.jpg

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