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.
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.