The present study was conducted to assess the effect of all-trans retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were excised from the knees of healthy adult Wistar female rats under sterile conditions. We first investigated the synoviums incubated in a control medium or in a medium containing 10 mg/mL LPS, each for 24, 48, and 72 h (LPS-experiment). The changes in inflammatory response from the synoviums were observed at different culture times. Then, we assessed the synoviums exposed to different ATRA concentrations for 24 h (ATRA-experiment). The controls (blank, model group, and solvent groups) were set up. The effects of ATRA on synovitis were evaluated by measuring the production of cytokines, and nitric oxide (NO) and the expression of cartilage damage related proteases. In the LPS-experiment, LPS contributed to the release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-a), and matrix metalloproteinase-9 (MMP-9) in synovial explants. Importantly, LPS did not cause a significant pathological damage. The inflammatory response observed in this model was significant for 24 h, suggesting that LPS-induced synovial explants were successfully established. In the ATRA-experiment, ATRA suppressed the expression of IL-6, TNF-a, NO, a disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS-4), MMP-3, and MMP-9. Taken together, ATRA exhibited inhibitory effects on LPS-induced synovial immune inflammatory response stimulated by the regulation of inflammatory mediators and cartilage damage related proteases in synovial explants, demonstrating a potential protective effect on synovitis and joint destruction in the patients with RA.
Current studies focused on the effects of all-trans-retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were extracted aseptically from the quadriceps femoris of the knee joint of rats, and then incubated in medium containing 10% neonate bovine serum for 24 h adaptive culture. We first measured variations of correlation factors in synovium at 24, 48, 72, 96 and 120 h in control medium or in medium containing 20 ng/mL tumor necrosis factor alpha (TNF-a) (TNF-a-experiment). Then, we investigated the synovium exposed to three ATRA concentrations after 48 h incubation (ATRA-experiment). The effects of ATRA on synovitis were evaluated by observing the expression of inflammatory cytokines, angiogenic factors and the production of proteases in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and apoptosis and autophagy. In TNF-a-experiment, the secretion of nitric oxide (NO), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) increased significantly after TNF-a stimulation without pathological damage to the synovium. Hence, we successfully obtained the synovial explants model, which had longer inflammatory response time. In the ATRA-experiment, ATRA suppressed the secretion of IL-6 and NO, downregulated the NF-kB P65 and Bcl-2, increased levels of autophagy marker protein LC3, but different doses of ATRA showed inconsistent regulatory effects on VEGF and MMP-9. In short, ATRA inhibited TNF-a induced synovitis by the regulation of inflammatory cytokines and inhibiting NF-kB signal transduction and potentially promoting autophagy, apoptosis and angiogenesis, displaying its role in alleviating synovial inflammation in patients with RA.
By employing bibliometric method, this study aimed to visualize the research hotspots and correlations among clinical medicine subjects. Literatures were retrieved from the PubMed database based on MeSH words and free-text phrases and screened based on inclusion and exclusion criteria. The disease themes were manually marked according to ICD-10. Co-word analysis and strategic diagram methods were applied to explore the hot topics and development trends of disease themes. 2551 articles were included after literature screening. The amount of paper showed an increasing trend and reached a peak in 2013. The subjects of adults and the elderly accounted for 45.0% and 27.0% respectively. The United States of America had the most publication, with Massachusetts and California being the most prevalent states, and Harvard University was the most prolific institution. Co-word analysis revealed that research hot topics of diseases were divided into 8 themes, among which the most was “disease of the circulatory system” and “injury, poisoning and certain other consequences of external causes”. The strategic diagram showed that the above two topics were mature but relatively independent, while the “physical fitness” topic was not mature enough but was closely related to the others. There are more and more data-driven studies in the field of medicine and health, while, huge development spaces in the full spectrum of the diseases do exist. Mining the published researches through bibliometrics and visualized methods could come up with valuable results to inform further study.
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