1,25-Dihydroxyvitamin D3 Inhibits the RANKL Pathway and Impacts on the Production of Pathway-Associated Cytokines in Early Rheumatoid Arthritis

Objectives. To study effects of 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) on RANKL signaling pathway and pathway-associated cytokines in patients with rheumatoid arthritis (RA). Methods. Receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), IFN-γ, IL-6, TNF-α, IL-17, and IL-4 were examined in 54 patients with incipient RA using a cytometric bead array (CBA) or an enzyme-linked immunosorbent assay (ELISA). Results. After 72 hours of incubation of peripheral blood mononuclear cells (PBMCs) with 1,25(OH)(2)D(3) in RA patients, the levels of RANKL, TNF-α, IL-17 and IL-6 significantly decreased compared to those of the control. 1,25(OH)(2)D(3) had no significantly impact on the levels of OPG, RANKL/OPG, and IL-4. Conclusions. The present study demonstrated that 1,25(OH)(2)D(3) reduced the production of RANKL and the secretion of TNF-α, IL-17, and IL-6 in PBMCs of RA patients, which indicated that 1,25(OH)(2)D(3) might be able to decrease damage of cartilage and bone in RA patients by regulating the expression of RANKL signaling pathway and pathway-associated cytokines.