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The therapeutic mechanisms of methotrexate in RA include: inhibition of dihydrofolate reductase to reduce nucleic acid production and promote cell death (78), downregulation of Th1 cells and upregulation of Th2 cells and Tregs (79), amelioration of bone destruction by increasing osteoprotegerin (OPG) and decreasing RANKL (80), suppression of osteoclast differentiation (92), and inhibition of MMP expression and cartilage matrix absorption (93)

Furthermore, in the studies by Borgstrm et al

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Downregulation of protein kinase C by phorbol ester treatment abolishes the synergistic effect of AVP on ACTH release by CRH (68)

When the body overproduces uric acid, or the kidneys struggle to remove it from the blood, it can accumulate and settle in the joints