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比较分析 CX3CL1(趋化因子)及其受体 CX3CR1 在血友病性关节病和骨关节炎中的发生和作用。

Comparative Analysis of the Occurrence and Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Hemophilic Arthropathy and Osteoarthritis.

机构信息

Department of General and Experimental Pathology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Pawińskiego 3C, 02-106 Warsaw, Poland.

Department of Rehabilitation, Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637 Warsaw, Poland.

出版信息

J Immunol Res. 2020 Aug 20;2020:2932696. doi: 10.1155/2020/2932696. eCollection 2020.

Abstract

OBJECTIVE

Hemophilic arthropathy is characterized by recurrent bleeding episodes in patients with hemophilia leading to irreversible joint degeneration. The involvement of CX3CL1 (fractalkine) and its receptor CX3CR1 was observed in the pathogenesis of numerous arthritis-associated diseases. Taking this into account, we have presented a study investigating the role of the CX3CL1/CX3XR1 axis in the course of hemophilic arthropathy, including the CX3CL1-dependent expression of CD56, CD68, and CD31 cells along with evaluation of articular cartilage and synovial membrane morphology.

METHODS

The study was carried out using cases ( = 20) of end-stage hemophilic arthropathy with a severe type of hemophilia A and control cases ( = 20) diagnosed with osteoarthritis. The biofluids including blood serum and synovial fluid were obtained intraoperatively for the evaluation of CX3CL1 using the ELISA test. Tissue specimens including articular cartilage and synovial membrane were similarly collected during surgery and stained immunohistologically using selected antibodies including anti-CX3CR1, anti-CD56, anti-CD68, and anti-CD31. Additionally, the analysis included the assessment of articular cartilage, synovial membrane, and blood vessel morphology.

RESULTS

In our study, we have documented increased average concentration of CX3CL1 in the blood serum of the study group (7.16 ± 0.53 ng/ml) compared to the control group (5.85 ± 0.70 ng/ml) without statistically significant difference in synovial fluid concentration at the same time. We have observed an increased macrophage presence with more marked proliferation and fibrosis of the synovial membrane in the study group. Remaining results such as expression of CX3CR1 presence of NK cells and larger surface area of blood vessels within the synovial membrane were noted also without statistical significance.

CONCLUSIONS

This study has demonstrated collective CX3CL1/CX3CR1 axis involvement in hemophilic arthropathy pathogenesis introducing new interesting diagnostics and a therapeutic target.

摘要

目的

血友病性关节病的特征是患者反复出血,导致关节不可逆退化。在许多与关节炎相关的疾病的发病机制中观察到了 CX3CL1(趋化因子)及其受体 CX3CR1 的参与。考虑到这一点,我们进行了一项研究,调查了 CX3CL1/CX3XR1 轴在血友病性关节病发病机制中的作用,包括 CX3CL1 依赖性表达 CD56、CD68 和 CD31 细胞,以及评估关节软骨和滑膜膜的形态。

方法

该研究使用了 20 例终末期血友病性关节病病例( = 20)和 20 例诊断为骨关节炎的对照病例。术中从血液血清和滑膜液中获得生物流体,使用 ELISA 试验评估 CX3CL1。在手术中同样收集关节软骨和滑膜膜等组织标本,使用选定的抗体进行免疫组织化学染色,包括抗 CX3CR1、抗 CD56、抗 CD68 和抗 CD31。此外,分析包括评估关节软骨、滑膜膜和血管形态。

结果

在我们的研究中,我们记录了研究组血液血清中 CX3CL1 的平均浓度增加(7.16 ± 0.53ng/ml),与对照组相比(5.85 ± 0.70ng/ml),但同时滑膜液浓度无统计学差异。我们观察到研究组中巨噬细胞增多,滑膜膜增殖和纤维化更明显。还观察到 CX3CR1 表达、NK 细胞存在和滑膜膜内血管表面积增大等其他结果,但无统计学意义。

结论

这项研究表明,集体 CX3CL1/CX3CR1 轴参与了血友病性关节病的发病机制,为新的有趣的诊断和治疗靶点提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35da/7455839/7cc5f6b25597/JIR2020-2932696.001.jpg

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