Abstract

Coronavirus disease 2019 (COVID-19) poses a serious threat to human health. To date, predicting the course of chronic diseases in individuals who suffered from a coronavirus infection is a topical issue. Osteoarthritis is a chronic degenerative disease of the joints. It was demonstrated that this disease can be caused by different factors, namely, the effect of oxidative stress, hypercholesterolemia, increased aggrecan-degrading activity of specific proteinases against the background of a disorder of particular endocytic pathway, etc. Therefore, the aim of this work was to analyze the expression of the OLR1, ACAN, and LRP1 genes in the synovial membrane cells in patients with osteoarthritis after SARS-CoV2 infection. The study involved 60 men aged 50 to 55. The volunteers were divided into the following groups: the first group (n = 20), conditionally healthy individuals; the second group (n = 20), patients with knee joint osteoarthritis of II–III degree; the third group consisted of 20 patients with knee joint osteoarthritis of II–III degree who recovered from COVID-19. A concentration of cholesterol in the human blood plasma was determined by the enzymatic method using a diagnostic reagent kit. The intensity of superoxide anion radical generation in the synovial fluid was measured by the accumulation of XTT-formazan. The level of expression of the OLR1, ACAN, and LRP1 genes in the synovial membrane cells of knee joints was determined using quantitative real-time RT-PCR. An increase in the expression level of the OLR1 gene was found to a greater extent in the synovial membrane cells in patients with osteoarthritis who recovered from COVID-19 as compared with the group of patients with knee joint osteoarthritis against the background of a more intensive increase in both the cholesterol concentration in the blood plasma and the activation of free radical processes (an increase in the content of superoxide anion radical) in the synovial fluid of patients with osteoarthritis after SARS-CoV2 infection. This can be associated with an increase in system-wide inflammation as a result of the organism’s response to a virus. At the same time, a more significant decrease in the level of the ACAN gene expression in the synovial membrane cells in patients with osteoarthritis who recovered from COVID-19 was demonstrated as compared with the group of patients with knee joint osteoarthritis. This indicates a more powerful activation of destructive processes in the cells after infection and can also be mediated by a decrease in the expression level of the LRP1 gene, which, in turn, can cause a further progression of the disease. Understanding of clear mechanisms for the formation of a more severe course of osteoarthritis and possible development of complications in patients with post-COVID-19 syndrome on the example of the functioning of both the LOX1/ox-LDL system and LRP1-endocytic pathway requires further studies.

中文翻译：

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SARS-CoV2感染后骨关节炎患者滑膜细胞中OLR1、ACAN和LRP1基因的表达

摘要

2019 年冠状病毒病 (COVID-19) 对人类健康构成严重威胁。迄今为止，预测冠状病毒感染者的慢性病病程是一个热门话题。骨关节炎是关节的一种慢性退行性疾病。已证明该疾病可由不同因素引起，即氧化应激、高胆固醇血症、在特定内吞途径紊乱的背景下特定蛋白酶的聚集蛋白聚糖降解活性增加等。因此，本研究的目的工作是分析OLR1、ACAN和LRP1的表达SARS-CoV2感染后骨关节炎患者滑膜细胞中的基因。该研究涉及 60 名 50 至 55 岁的男性。志愿者分为以下几组：第一组（n = 20），有条件的健康个体；第二组（n =20），Ⅱ～Ⅲ度膝关节骨性关节炎患者；第三组由 20 名从 COVID-19 康复的 II-III 度膝关节骨关节炎患者组成。使用诊断试剂盒通过酶法测定人血浆中的胆固醇浓度。滑液中超氧阴离子自由基生成的强度通过 XTT-甲臜的积累来测量。OLR1、ACAN的表达水平，以及膝关节滑膜细胞中的LRP1基因是使用定量实时 RT-PCR 确定的。OLR1表达水平的增加在血浆中胆固醇浓度显着增加的背景下，与膝关节骨关节炎患者组相比，从 COVID-19 康复的骨关节炎患者的滑膜细胞中发现了更大程度的基因SARS-CoV2感染后骨关节炎患者滑液中自由基过程的激活（超氧阴离子自由基含量增加）。由于生物体对病毒的反应，这可能与全身炎症的增加有关。同时，ACAN 水平下降更显着与膝关节骨关节炎患者组相比，从 COVID-19 康复的骨关节炎患者的滑膜细胞中的基因表达得到证实。这表明感染后细胞中的破坏性过程被更强大地激活，并且也可以通过 LRP1 基因表达水平的降低来介导，这反过来又会导致疾病的进一步发展。以 LOX1/ox-LDL 系统和 LRP1 内吞途径的功能为例，了解更严重的骨关​​节炎病程形成的明确机制以及 COVID-19 后综合征患者可能发生并发症的机制需要进一步学习。