Inhibition of CRLF1 expression by miR-8485 alleviates IL-1β-induced chondrocyte inflammation, apoptosis, and extracellular matrix degradation

IF 4.8 2区 医学 Q2 IMMUNOLOGY
Guang Yang , Bingzhou Ji , Hengzhen Li , Xiu liu , Gaoming Liu , Jianfeng Sun , Yuming Yao , Yusheng Li , Shuguang Liu , Wenfeng Xiao
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引用次数: 0

Abstract

The aim of this study was to investigate the impact of differentially expressed miR-8485 on chondrocyte inflammation in osteoarthritis (OA) and its underlying pathological mechanisms. MiR-8485, which was downregulated in OA, was identified by microarray analysis, and was also found to be decreased in IL-1β-induced C28/I2 cells. miR-8485 down-regulation or IL-1β treated of C28/I2 cells induces a decrease in cellular activity, an increase in apoptosis, an elevation in Cleaved caspase-3, MMP13, and ADAMTS5 protein levels, a decrease in Collagen II and Aggrecan levels, and an increase in the levels of pro-inflammatory factors TNF-α and IL-6. CRLF1 was identified to be a downstream target gene of miR-8485 using bioinformatics prediction and dual luciferase reporter gene assays. CRLF1 was shown to be increased in IL-1β-treated C28/I2 cells, and CRLF1 overexpression partially abrogated the suppressive effect of upregulated miR-8485 on chondrocyte inflammation. In addition, miR-8485 was able to inhibit MAPK/ERK and PI3K/AKT signaling activation by inhibiting CRLF1. In conclusion, miR-8485 was able to inhibit CRLF1 expression and thus inhibit IL-1β-triggered inflammation in chondrocytes, potentially through the inhibition of MAPK/ERK and PI3K/AKT signaling pathways.
miR-8485 可抑制 CRLF1 的表达,减轻 IL-1β 诱导的软骨细胞炎症、凋亡和细胞外基质降解。
本研究旨在探讨差异表达的 miR-8485 对骨关节炎(OA)软骨细胞炎症的影响及其潜在的病理机制。通过微阵列分析确定了在 OA 中下调的 miR-8485,并发现其在 IL-1β 诱导的 C28/I2 细胞中也有所下降。miR-8485 下调或 IL-1β 处理 C28/I2 细胞会诱导细胞活性下降、细胞凋亡增加、Cleaved caspase-3、MMP13 和 ADAMTS5 蛋白水平升高、胶原蛋白 II 和 Aggrecan 水平下降以及促炎因子 TNF-α 和 IL-6 水平升高。通过生物信息学预测和双荧光素酶报告基因检测,CRLF1 被确定为 miR-8485 的下游靶基因。研究表明,CRLF1在IL-1β处理的C28/I2细胞中增加,CRLF1的过表达部分减弱了上调的miR-8485对软骨细胞炎症的抑制作用。此外,miR-8485 还能通过抑制 CRLF1 来抑制 MAPK/ERK 和 PI3K/AKT 信号的激活。总之,miR-8485 能够抑制 CRLF1 的表达,从而抑制 IL-1β 触发的软骨细胞炎症,这可能是通过抑制 MAPK/ERK 和 PI3K/AKT 信号通路实现的。
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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