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纤维蛋白原α的差异表达及其在骨关节炎发病机制中的潜在作用

Differential Expression of Fibrinogen Alpha and Its Potential Involvement in Osteoarthritis Pathogenesis.

作者信息

Kumavat Rajkamal, Kumar Vijay, Biswas Sagarika

机构信息

Council of Scientific &Industrial Research (CSIR) - Institute of Genomics & Integrative Biology, Mall Road, Delhi University Campus, 110007, Delhi, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.

出版信息

Mol Biotechnol. 2025 Jan;67(1):104-114. doi: 10.1007/s12033-023-00983-w. Epub 2024 Jan 5.

DOI:10.1007/s12033-023-00983-w
PMID:38182865
Abstract

The deterioration of cartilage tissue and other joint components composed of synovial tissue is a defining characteristic of osteoarthritis (OA) disease. Because of the lack of understanding of the underlying cause and important molecular pathways, there are currently no effective diagnostic or treatment methods for OA. The purpose of the study is to find a specific protein biomarker with high sensitivity and specificity in order to understand the pathophysiology of the disease and the underlying molecular pathways. We examined plasma samples of matched age and sex from OA patients (n = 150) and healthy controls (HC) (n = 70) to find proteins that were differentially expressed and validated by western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence. The results of western blotting demonstrated that the expression level of the fibrinogen alpha (FGA) protein was higher in plasma samples of osteoarthritis (OAPL) (p = 0.0343), and the ROC (receiver operating characteristic curve) curve supported the high sensitivity (95.22%) and specificity (74%) of FGA in OA plasma compared to healthy controls. FGA protein was detected to be deposited in the synovial tissue of OA patients (p = 0.0073). By activating the Toll-like receptor (TLR-4) receptor pathway in PBMCs (p = 0.04) and synovial tissue, FGA protein may be involved in the molecular mechanism of OA pathogenesis. Our findings collectively suggested that FGA, which is significantly expressed in OA plasma, synovial tissue, and PBMCs and is connected to the disease's advancement through the TLR-4 receptor, may serve as a diagnostic or disease-evolving tool for OA.

摘要

软骨组织以及由滑膜组织构成的其他关节成分的退化是骨关节炎(OA)疾病的一个决定性特征。由于对其潜在病因和重要分子途径缺乏了解,目前尚无针对OA的有效诊断或治疗方法。本研究的目的是找到一种具有高敏感性和特异性的特定蛋白质生物标志物,以了解该疾病的病理生理学和潜在分子途径。我们检测了年龄和性别匹配的OA患者(n = 150)和健康对照(HC)(n = 70)的血浆样本,以寻找差异表达的蛋白质,并通过蛋白质印迹法、酶联免疫吸附测定(ELISA)、免疫组织化学和免疫荧光进行验证。蛋白质印迹法的结果表明,骨关节炎患者血浆样本(OAPL)中纤维蛋白原α(FGA)蛋白的表达水平更高(p = 0.0343),并且ROC(受试者工作特征曲线)曲线支持FGA在OA血浆中相对于健康对照具有高敏感性(95.22%)和特异性(74%)。检测到FGA蛋白沉积在OA患者的滑膜组织中(p = 0.0073)。通过激活PBMCs(p = 0.04)和滑膜组织中的Toll样受体(TLR - 4)受体途径,FGA蛋白可能参与OA发病机制的分子机制。我们的研究结果共同表明,FGA在OA血浆、滑膜组织和PBMCs中显著表达,并通过TLR - 4受体与疾病进展相关,可能作为OA的诊断或疾病进展监测工具。

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本文引用的文献

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