COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration.

COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration.
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DOI:
10.3389/fgene.2021.721258
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发表时间:
2021
影响因子:
3.7
通讯作者:
Yin L
Yin L
中科院分区:
生物学3区
文献类型:
--
作者:
Li S;Wang H;Zhang Y;Qiao R;Xia P;Kong Z;Zhao H;Yin L

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骨关节炎(OA)是最常见的与年龄相关的退行性疾病之一。近年来的研究表明,OA滑膜的病理改变早于软骨。然而,滑膜炎在OA病理过程中的分子机制尚未阐明。本研究旨在鉴定与OA相关的新生物标志物,并强调免疫细胞在OA发病机制中的作用。微阵列数据集从Gene Expression Omnibus(GEO)和ArrayExpress数据库获得,然后使用R软件进行分析。为了确定差异免疫细胞亚型浸润,使用CIBERSORT去卷积算法。使用定量逆转录PCR(qRT-PCR)来确定所选基因的相对表达。Western blotting检测软骨细胞蛋白表达水平。在分析数据库概况后,发现了与OA相关的两种潜在生物标志物,胶原3型α 1链(COL 3A 1)和基质金属蛋白酶9(MMP 9),并通过qRT-PCR和Western印迹法证实。具体而言,结果显示,随着IL-1β浓度的增加,COL 3A 1和MMP 9的基因和蛋白表达水平也增加。这些发现为未来研究OA免疫治疗和诊断的新靶点提供了有价值的信息和方向,并有助于发现OA发病机制的潜在生物学机制。
Osteoarthritis (OA) is one of the most common age-related degenerative diseases. In recent years, some studies have shown that pathological changes in the synovial membrane occur earlier than those in the cartilage in OA. However, the molecular mechanism of synovitis in the pathological process of OA has not been elucidated. This study aimed to identify novel biomarkers associated with OA and to emphasize the role of immune cells in the pathogenesis of OA. Microarray datasets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases and were then analyzed using R software. To determine differential immune cell subtype infiltration, the CIBERSORT deconvolution algorithm was used. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expressions of selected genes. Besides, Western blotting was used to assess the protein expression levels in osteoarthritic chondrocytes. After analyzing the database profiles, two potential biomarkers, collagen type 3 alpha 1 chain (COL3A1), and matrix metalloproteinase 9 (MMP9), associated with OA were discovered, which were confirmed by qRT-PCR and Western blotting. Specifically, the results revealed that, as the concentration of IL-1β increased, so did the gene and protein expression levels of COL3A1 and MMP9. The findings provide valuable information and direction for future research into novel targets for OA immunotherapy and diagnosis and aids in the discovery of the underlying biological mechanisms of OA pathogenesis.
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