Paradoxically, IL-4 correlates with hand VC severity and all-cause mortality in rheumatoid arthritis (RA) patients (HR = 1.41, 95% CI 1.12, 1.78; P = 0.004) (65), yet short-term IL-4 exposure upregulates osteoprotegerin (OPG) via STAT6 to inhibit calcification, whereas chronic exposure induces Cbfa1-mediated osteogenic differentiation (66). The gene discussed is RUNX2; the disease is rheumatoid arthritis.