SPP1 and rheumatoid arthritis: Therefore, OPN acts as an important mediator in the maintenance of RA, as it activates synovial macrophages and fibroblasts, which stimulate cartilage and bone matrix degradation by secreting matrix MPPs and pro-inflammatory cytokines such as IL-6 and TNF-α in addition to stimulating fibrosis [73,75,76,81,82,83].