Promoter Methylation of WIF1 is Involved in IL-17-Induced Chondrocyte Inflammatory Injury and Matrix Degradation via Promoting Wnt5a/MAPK-JNK Signaling.
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Abstract
The activity of Wnt inhibitory factor 1 (WIF1) is reduced upon promoter methylation and is involved in cartilage degradation in osteoarthritis. This study aims to investigate the mechanism by which WIF1 methylation is involved in chondrocyte damage in ankylosing spondylitis (AS). A model of chondrocyte inflammatory injury in AS was constructed by stimulation with interleukin (IL)-17. WIF1 level in injured chondrocytes was detected by western blot and RT-qPCR. ELISA kits were used to assess the levels of inflammatory cytokines. The expressions of MMP9, MMP13, collagen II, and ADAMTS-4 were tested by western blot and RT-qPCR. Wnt5a/mMAPK signaling and associated phosphorylated protein expressions were observed using western blot. After overexpression of Wnt5a, the same assays were used to evaluate the above indexes. The methylation level of the WIF1 promoter was measured by MSP-PCR assay. WIF1 expression declined in IL-17-induced chondrocytes. Overexpression of WIF1 decreased the levels of inflammatory factors TNFα, IL-1β, and IL-6, as well as downregulated the expressions of MMP9, MMP13, collagen II, and ADAMTS-4. Likewise, elevated WIF1 inhibited the Wnt5a/MAPK signaling and phosphorylation of JNK. However, upregulation of Wnt5a in IL-17-treated chondrocytes attenuated these responses. Besides, in damaged chondrocytes, WIF1 expression was reduced due to promoter methylation, while it was upregulated after demethylation. In summary, WIF1 exhibits high methylation levels in AS and is involved in inflammatory injury and matrix degradation in chondrocytes by regulating the Wnt5a/MAPK-JNK pathway.
期刊介绍：
Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.
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