Osteoarthritis (OA) is a degenerative joint disease usually seen in the elderly, which incidence increases with age. Its pathogenesis and underlying mechanism are still unclear. The disease severely affects the physical health and life quality of patients, thereby constituting a huge economic burden to family and society. Luteolin (LUT) is a natural flavonoid with multiple pharmacological properties. Many plants containing LUT have been applied in the treatment of several inflammation-related diseases due the relatively strong anti-inflammatory effects of LUT. The present study investigated the influence of LUT on cell apoptosis and inflammatory reactions in cartilage of OA guinea pigs, and its underlying mechanism. It was found that LUT effectively inhibited proliferation of OA cartilage cells, down-regulated the expressions of JNK and p38MAPK in cartilage cells of OA, and downregulated NO, TNF-α and IL-6. Thus, it alleviated inflammatory reactions, protected cartilage cells, and delayed cartilage degeneration.

Ellagic acid (EA) was reported to play protective roles in rheumatoid arthritis (RA). It was found that the level of metastasis-associated gene 1 (MTA1)/histone deacetylase 1 (HDAC1) protein complex was downregulated by polyphenols in several human disorders. Notably, inhibition of MTA1 or HDAC1 has anti-inflammatory effects on RA. Therefore, our study is aimed at investigating whether EA prevents RA progression through regulating the MTA1/HDAC1 complex. Herein, the human fibroblast-like synoviocyte (FLS) cell line MH7A was treated with TNF-α to induce an inflammation model in vitro and then incubated with different concentrations of EA. Western blot analysis showed that EA reduced MTA1 expression in a dose-dependent manner in MH7A cells. Then, TNF-α-treated MH7A cells were incubated with EA alone or together with MTA1 overexpression plasmid (pcDNA-MTA1), and we found that EA inhibited proliferation, inflammation cytokine levels, and oxidative stress marker protein levels and promoted apoptosis in MH7A cells, while MTA1 overexpression abolished these effects. Moreover, coimmunoprecipitation assay verified the interaction between MTA1 and HDAC1. EA downregulated the MTA1/HDAC1 complex in MH7A cells. MTA1 knockdown inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells, while HDAC1 overexpression reversed these effects. Moreover, chromatin immunoprecipitation assay indicated that EA inhibited HDAC1-mediated Nur77 deacetylation. Rescue experiments demonstrated that Nur77 knockdown reversed the effects of EA on MH7A cell biological behaviors. Additionally, EA treatment attenuated arthritis index, paw swelling, synovial hyperplasia, and inflammation in collagen-induced arthritis (CIA) rats. In conclusion, EA inhibited proliferation, inflammation, and oxidative stress and promoted apoptosis in MH7A cells and alleviated the severity of RA in CIA rats though downregulating MTA1/HDAC1 complex and promoting HDAC1 deacetylation-mediated Nur77 expression.

rheumatoid arthritis (ra) and osteoarthritis (oa) are the two most common debilitating joint disorders and although both share similar clinical manifestations, the pathogenesis of each is different and remains relatively unclear. The present study aimed to use bioinformatic analysis to identify pivotal genes and pathways involved in the pathogenesis of ra. Microarray datasets from patients with ra and oa were obtained from the Gene expression omnibus (Geo) database and differentially expressed genes (deGs) were identified using GEO2R software; Gene Ontology analysis and pathway enrichment were analyzed using the database for annotation, Visualization and integrated discovery and the Kyoto Encylopedia for Genes and Genomes, respectively; and protein-protein interaction networks of deGs were constructed using the Search Tool for the retrieval of interacting Genes database, and module analysis and pathway crosstalk of the PPi network was visualized using plugins of cytoscape. in addition, the prediction of target mrnas for differentially expressed micrornas (deMs) was performing using the star-Base database and the identified pivotal genes were verified using reverse-transcription quantitative Pcr in synovial tissue from patients with RA. A total of 566 DEGs were identified in GSe55457, GSe55235 while 23 DEMs were identified in the GSe72564 dataset. upregulated deGs were found to be mostly enriched in the 'cytokine-cytokine receptor interaction' pathway, whereas downregulated deGs were discovered to be enriched in the 'PPar signaling pathway'. The top 25 deGs were mostly enriched in the 'chemokine signaling pathway'. in addition, six of the mirna target genes were selected as potential biomarkers and a total of 24 genes were selected as potential hub genes. experimental validation demonstrated that the expression levels of cytotoxic T-lymphocyte associated Protein 4 (CTLA4), Zeta-chain-associated protein kinase 70 (ZAP70) and lcK proto-oncogene (LCK) were significantly increased, whereas HGF expression levels were decreased in RA synovial tissue. In conclusion, these findings suggest that the identified deGs and pivotal genes in the present study may further enhance our knowledge of the underlying pathways in the pathogenesis of ra. These genes may also serve as diagnostic biomarkers and therapeutic targets for RA; however, further experimental validation is necessary following the bioinformatic analysis to determine our conclusions.

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