IL-1 Receptor Antagonist Anakinra Inhibits the Effect of IL-1β- Mediated Osteoclast Formation by Periodontal Ligament Fibroblasts.

IF 3.6 3区 生物学 Q1 BIOLOGY
Elizabeth Steemers, Wael M I Talbi, Jolanda M A Hogervorst, Ton Schoenmaker, Teun J de Vries
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引用次数: 0

Abstract

Rheumatoid arthritis and periodontitis are comorbidities that share mutual pathways. IL-1β is a pro-inflammatory cytokine that plays a crucial role in both diseases. One of the treatment options for rheumatoid arthritis is the use of an IL-1 receptor antagonist (IL-1RA) such as anakinra. Anakinra tempers the disease by decreasing bone resorption and it could possibly stimulate bone formation. Here, we investigate the effect of anakinra in a periodontal disease setting on osteoclastogenesis by co-culturing periodontal ligament fibroblasts (PDLFs) and peripheral blood mononuclear cells (PBMCs) that contain monocytes, a source of osteoclast precursors, as well as by culturing PBMCs alone. The effect of anakinra on PDLF-mediated osteogenesis was studied under mineralization conditions. To mimic a chronic infection such as that prevalent in periodontitis, 10 ng/mL of IL-1β was added either alone or with 10 µg/mL of anakinra. Osteoclastogenesis experiments were performed using co-cultures of PDLF and PBMCs and PBMCs only. Osteoclastogenesis was determined through the formation of multinucleated cells in co-cultures of PDLF and PBMCs, as well as PBMCs alone, at day 21, and gene expression through qPCR at day 14. Osteogenesis was determined by measuring alkaline phosphatase activity (ALP) per cell at day 14. Anakinra is effective in downregulating IL-1β mediated leukocyte clustering and osteoclastogenesis in the co-cultures of both PDLF and PMBCs and PBMCs alone. Gene expression analysis shows that IL-1β increases the expression of the osteoclastogenic marker RANKL and its own expression. This higher expression of IL-1β at the RNA level is reduced by anakinra. Moreover, IL-1β downregulates OPG expression, which is upregulated by anakinra. No effects of anakinra on osteogenesis were seen. Clinically, these findings suggest that anakinra could have a beneficial systemic effect on periodontal breakdown in rheumatoid arthritis patients taking anakinra.

IL-1受体拮抗剂Anakinra抑制IL-1β介导的牙周韧带成纤维细胞形成破骨细胞的作用。
类风湿关节炎和牙周炎是具有共同途径的合并症。IL-1β是一种促炎细胞因子,在这两种疾病中都起着至关重要的作用。类风湿性关节炎的治疗选择之一是使用IL-1受体拮抗剂(IL-1RA),如阿那金。Anakinra通过减少骨吸收来缓解疾病,它可能会刺激骨形成。在这里,我们通过共同培养牙周韧带成纤维细胞(PDLFs)和含有单核细胞(破骨细胞前体的来源)的外周血单核细胞(PBMCs)以及单独培养PBMCs,研究了anakinra在牙周病环境下对破骨细胞形成的影响。在矿化条件下,研究了阿那白对pdlf介导的成骨作用。为了模拟慢性感染,如牙周炎中普遍存在的感染,单独添加10 ng/mL的IL-1β或与10 μ g/mL的anakinra一起添加。破骨细胞生成实验采用ppdf和PBMCs共培养和仅PBMCs共培养进行。在第21天,通过ppdf和PBMCs共培养以及单独PBMCs共培养的多核细胞的形成,以及在第14天通过qPCR的基因表达来确定破骨细胞的发生。第14天,通过测定每个细胞的碱性磷酸酶活性(ALP)测定成骨情况。Anakinra可以有效下调IL-1β介导的白细胞聚集和破骨细胞生成,在ppdf和pmbc共培养和单独PBMCs中。基因表达分析显示,IL-1β增加破骨细胞标志物RANKL的表达及自身表达。在RNA水平上IL-1β的高表达被阿那白素降低。此外,IL-1β下调OPG的表达,而anakinra上调OPG的表达。未见安纳白那对成骨的影响。临床研究结果表明,阿那白对类风湿关节炎患者服用阿那白对牙周破坏有有益的全身性影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biology-Basel
Biology-Basel Biological Science-Biological Science
CiteScore
5.70
自引率
4.80%
发文量
1618
审稿时长
11 weeks
期刊介绍: Biology (ISSN 2079-7737) is an international, peer-reviewed, quick-refereeing open access journal of Biological Science published by MDPI online. It publishes reviews, research papers and communications in all areas of biology and at the interface of related disciplines. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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