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白细胞介素-6受体阻滞剂萨瑞鲁单抗对原代人成骨细胞代谢活性和分化能力的影响

Effects of the Interleukin-6 Receptor Blocker Sarilumab on Metabolic Activity and Differentiation Capacity of Primary Human Osteoblasts.

作者信息

Klinder Annett, Waletzko-Hellwig Janine, Sellin Marie-Luise, Seyfarth-Sehlke Anika, Wolfien Markus, Prehn Franziska, Bader Rainer, Jonitz-Heincke Anika

机构信息

Research Laboratory for Biomechanics and Implant Technology, Department of Orthopedics, Rostock University Medical Centre, 18057 Rostock, Germany.

Department of Systems Biology and Bioinformatics, University of Rostock, 18057 Rostock, Germany.

出版信息

Pharmaceutics. 2022 Jun 30;14(7):1390. doi: 10.3390/pharmaceutics14071390.

DOI:10.3390/pharmaceutics14071390
PMID:35890286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9318132/
Abstract

Interleukin (IL-) 6 is a key factor in the inflammatory processes of rheumatoid arthritis. Several biologic agents target the IL-6 signaling pathway, including sarilumab, a monoclonal antibody that blocks the IL-6 receptor and inhibits IL-6-mediated cis- and trans-signaling. A careful analysis of the IL-6 signaling blockade should consider not only inflammatory processes but also the regenerative functions of IL-6. The purpose of this study was to investigate whether inhibition of the IL-6 receptors affects differentiation of human primary osteoblasts (hOB). The effects of sarilumab on viability and the differentiation capacity in unstimulated osteoblasts as well as after stimulation with various IL-6 and sIL6-R concentrations were determined. Sarilumab treatment alone did not affect the differentiation or induction of inflammatory processes in hOB. However, the significant induction of alkaline phosphatase activity which was observed after exogenous IL-6/sIL-6R costimulation at the highest concentrations was reduced back to baseline levels by the addition of sarilumab. The IL-6 receptor blockade also decreased gene expression of mediators required for osteogenesis and bone matrix maintenance. Our results demonstrate that concomitant administration of the IL-6 receptor blocker sarilumab can inhibit IL-6/sIL-6R-induced osteogenic differentiation.

摘要

白细胞介素（IL-）6是类风湿性关节炎炎症过程中的关键因子。几种生物制剂靶向IL-6信号通路，包括萨立鲁单抗，一种阻断IL-6受体并抑制IL-6介导的顺式和反式信号传导的单克隆抗体。对IL-6信号传导阻断的仔细分析不仅应考虑炎症过程，还应考虑IL-6的再生功能。本研究的目的是调查抑制IL-6受体是否会影响人原代成骨细胞（hOB）的分化。确定了萨立鲁单抗对未刺激的成骨细胞以及用各种IL-6和sIL6-R浓度刺激后的活力和分化能力的影响。单独使用萨立鲁单抗治疗不会影响hOB的分化或炎症过程的诱导。然而，在最高浓度的外源性IL-6/sIL-6R共刺激后观察到的碱性磷酸酶活性的显著诱导通过添加萨立鲁单抗降低回基线水平。IL-6受体阻断也降低了成骨和骨基质维持所需介质的基因表达。我们的结果表明，同时给予IL-6受体阻滞剂萨立鲁单抗可以抑制IL-6/sIL-6R诱导的成骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/11d7a0ff4b9f/pharmaceutics-14-01390-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/9132eefcee24/pharmaceutics-14-01390-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/7aa20d51b432/pharmaceutics-14-01390-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/7344db82cb69/pharmaceutics-14-01390-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/26f075a3ca44/pharmaceutics-14-01390-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/21faf558722e/pharmaceutics-14-01390-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/20e330b0346d/pharmaceutics-14-01390-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/11d7a0ff4b9f/pharmaceutics-14-01390-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/9132eefcee24/pharmaceutics-14-01390-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/7aa20d51b432/pharmaceutics-14-01390-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/7344db82cb69/pharmaceutics-14-01390-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/26f075a3ca44/pharmaceutics-14-01390-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/21faf558722e/pharmaceutics-14-01390-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/20e330b0346d/pharmaceutics-14-01390-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48b8/9318132/11d7a0ff4b9f/pharmaceutics-14-01390-g007.jpg

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2
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3
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Determination of Heterogeneous Proteomic and Metabolomic Response in anti-TNF and anti-IL-6 Treatment of Patients with Rheumatoid Arthritis.
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Biomolecules. 2020 Dec 31;11(1):48. doi: 10.3390/biom11010048.
4
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J Endocrinol. 2021 Feb;248(2):R51-R65. doi: 10.1530/JOE-20-0428.
5
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