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Osteoarthritis (OA), a most common and highly prevalent joint disease, is closely associated with dysregulated expression and modification of RXRα. However, the role of RXRα in the pathophysiology of OA remains unknown. The present study aimed to investigate whether RXRα modulator, such as K-80003 can treat OA. Experimental OA was induced by intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats. Articular cartilage degeneration was assessed using Safranin-O and fast green staining. Synovial inflammation was measured using hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA). Expressions of MMP-13, ADAMTS-4 and ERα in joints were analyzed by immunofluorescence staining. Western blot, RT-PCR and co-Immunoprecipitation (co-IP) were used to assess the effects of K-80003 on RXRα-ERα interaction. Retinoid X receptor α (RXRα) modulator K‐80003 prevented the degeneration of articular cartilage, reduced synovial inflammation, and alleviated osteoarthritic pain in rats. Furthermore, K-80003 markedly inhibited IL-1β‐induced p65 nuclear translocation and IκBα degradation, and down-regulate the expression of HIF-2α, proteinases (MMP9, MMP13, ADAMTS-4) and pro-inflammatory factors (IL-6 and TNFα) in primary chondrocytes. Additionally, knockdown of ERα with siRNA blocked these effects of K-80003 in chondrocytes. In conclusion, RXRα modulators K-80003 suppresses inflammatory and catabolic responses in OA, suggesting that targeting RXRα‐ERα interaction by RXRα modulators might be a novel therapeutic approach for OA treatment. [ABSTRACT FROM AUTHOR]

Our purpose was to investigate the effect of 3-deazaneplanocin A (DZNep) on human T-cell acute lymphoid leukemia (T-ALL) cells, and to explore the underlying molecular mechanisms. The human T-ALL cell line Molt4 was treated with DZNep, and cell proliferation was examined. The expression of Mps one binder kinase activator 1 gene (MOB1) mRNA and protein was determined by RT-PCR and Western blotting, respectively. The histone modification effect of DZNep on the lysine 9 of histone 3 associated with MOB1 promoters was examined with chromatin immunoprecipitation and quantitative PCR, and CpG methylation in MOB1 promoters was detected by bisulfite sequencing PCR. DZNep treatment inhibited the growth of Molt4 cells. The expressions of MOB1 genes were upregulated by DZNep treatment, and histone methylations in their promoters were significantly reduced. The results indicate that DZNep is a promising therapeutic compound for the treatment of human T-ALL. [ABSTRACT FROM AUTHOR]