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Receptor activator of nuclear factor κB ligand (RANKL) plays a crucial role in the bone erosion of rheumatoid arthritis (RA) by prompting osteoclastogenesis. Considering that 1,25(OH)2D3 has been suggested as a potent inducer of RANKL expression, it should clarify whether vitamin D supplement could result in RANKL overexpression and thereby facilitate excessive osteoclastogenesis and bone resorption in RA. Here, we investigated modulatory effect of 1,25(OH)2D3 on the expression of RANKL and its decoy receptor osteoprotegerin (OPG) in an inflammatory condition of human rheumatoid synoviocyte MH7A. MH7A cells were stimulated with IL1β and then treated with different concentrations of 1,25(OH)2D3 for 48 h. A significantly elevated OPG/RANKL ratio and markedly decreased levels of IL-6 and TNFβ mRNA expression in cells and IL-6 protein in supernatants were observed in IL1β-induced MH7A in the presence of 1,25(OH)2D3 compared with those in the absence of it. Osteoclast formation was obviously decreased when RAW264.7 cells were treated with both 1,25(OH)2D3 and IL1β. In summary, although it has a biological function to induce RANKL expression, 1,25(OH)2D3 could upregulate OPG/RANKL ratio and mediate anti-inflammatory action in an inflammatory milieu of synoviocyte, contributing to the inhibition of inflammation-induced osteoclastogenesis in RA.

Objective Interstitial lung disease (ILD) is a common extramuscular complication contributing to significant morbidity and mortality in anti-melanoma differentiation associated gene 5 positive dermatomyositis (anti-MDA5+ DM). We conducted this study to investigate the association of anti-Ro52 antibodies with clinical characteristics and prognosis in anti-MDA5+ DM patients. Methods We assessed a cohort of 246 patients with anti-MDA5+ DM. To calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for RP-ILD and death while controlling for potential confounders, variables selected by univariate COX regression analysis were included in a multivariate COX regression model with the stepwise forward selection method. A 2-tailed p value <0.05 was considered to indicate statistical significance. Results 246 anti-MDA5+ DM patients were enrolled, 70 cases male, with an average age of 53.10±12.35 years. Anti-Ro52 coexisted in 64.22% (158/246) patients. Anti- Ro52 autoantibodies positive anti-MDA5+ DM patients had a higher rate of RP-ILD (log-rank p<0.001) and a higher mortality rate (log-rankp=0.010). For anti-MDA5+ DM patients with positive anti-Ro52 antibodies, patients with a short disease course, and high inflammation are at increased risk of RP-ILD and death. The appearance of the active rash is an independent protective factor of death. Conclusion Anti-Ro52 antibodies are highly prevalent in anti-MDA5+ DM patients and their coexistence correlates with a higher rate of RP-ILD and mortality. Patients with a short disease course, increased inflammation and without rash are more likely to have a poor prognosis.