Selective inhibition of interleukin 6 receptor decreased inflammatory cytokines and increased proteases in an experimental model of critical calvarial defect.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI:10.1590/1414-431X2024e13913
R C O Melo, A A Martins, G H A Vieira, R V S Andrade, D N A Silva, J Chalmers, T M Silveira, F Q Pirih, V S Araújo, J S P Silva, M L D S Lopes, R F C Leitão, R F Araújo Júnior, I L G Silva, L J T Silva, E G Barbosa, A A Araújo
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引用次数: 0

Abstract

Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.

选择性抑制白细胞介素 6 受体可减少临界腓骨缺损实验模型中的炎症细胞因子并增加蛋白酶。
考虑到选择性 IL-6 受体抑制剂对骨重塑的影响尚未达成共识,且相关报道较少,尤其是针对大面积骨缺损的报道,本研究拟评估白细胞介素-6 受体选择性抑制剂(托珠单抗)在大鼠临界腓骨缺损实验模型中的生物学影响。在这项临床前和体内研究中,24 只雄性 Wistar 大鼠被随机分为两组(n=12/组):用海绵胶原处理缺损组(CG)和用海绵胶原联合 2 mg/kg 托西珠单抗处理缺损组(TCZ)。顶骨缺损是用直径为 8 毫米的穿刺钻造成的。90 天后,动物被安乐死,并通过显微 CT、组织学、免疫组化、细胞因子和 RT-qPCR 分析对组织样本(颅盖)进行评估。托西珠单抗减少了单核炎症浸润(P0.05)。两组缺损区的骨细胞(成骨细胞、破骨细胞和骨细胞)相似(P>0.05)。托西珠单抗可减少大鼠临界骨缺损处的炎性细胞因子,降低成骨蛋白,增加蛋白酶。在颅骨缺损处局部应用托西珠单抗九十天后,我们发现与胶原海绵相比,骨组织的形成并不明显。
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
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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