Uridine Diphosphate Promotes Rheumatoid Arthritis Through P2Y6 Activation

BACKGROUND: Uridine diphosphate (UDP) is an extracellular nucleotide signaling molecule implicated in diverse biological processes via specific activation of pyrimidinergic receptor P2Y, G Protein-Coupled, 6 (P2Y6). There very little knowledge about the function and mechanism UDP rheumatoid arthritis (RA). METHODS: This study used a quasi-targeted liquid chromatography-mass spectrometry (LC-MS) approach to investigate unique expression metabolites RA synovial fluids (SF) ( n = 10) with samples from osteoarthritis (OA) as controls 10). fibroblast-like synoviocytes (FLSs) were collected tissues 5) cultured or MRS2578, P2Y6 antagonist, FLSs OA 5). Rats collagen-induced (CIA) injected UDP, MRS2578 both 9 for each group). was examined using real-time PCR, Western blotting immunohistochemistry. Cell proliferation, apoptosis migration measured CCK-8 assay, cell analysis, flow cytometry, wound healing assay Transwell respectively. The levels culture medium, fluid 36) peripheral blood CIA rats Transcreener Assay. Levels proinflammatory cytokines assay. Interleukin-6 (IL-6) ELISA flow. RESULTS: LC-MS analysis detected significantly increased SF compared SF, level positively correlated anticyclic citrullinated peptide (anti-CCP) factor (RF)levels RA. concentration verified patients healthy volunteers, stimulated IL-6 secretion inhibited their culture, these effects UDP. injection accelerated production rather than other rat model, but simultaneous suppressed alleviated CIA. tissues. CONCLUSION: These results suggest that highly expressed stimulates pathogenesis by promoting activities increase production.