We delineated in RA chronic synovitis that the CD48hiS100A12+ and CD48+SPP1+ macrophage clusters produced their distinctive pathogenic mediators (S100A12 and SPP1, respectively) in addition to hallmark proinflammatory cytokines IL-6, IL-8, IL-1β, and TNF-α, and activated ST stromal cells. This evidence concerns the gene SPP1 and rheumatoid arthritis.