Macrophages in RA synovium show a significant M1/M2 polarization imbalance, with M1-type macrophages predominating and releasing large amounts of pro-inflammatory factors, such as TNF-α, IL-1β, IL-6, etc. These cytokines not only directly stimulate OC precursor cell differentiation, but also activate FLSs and promote their secretion of RANKL and MMPs, which further exacerbate bone resorption and cartilage degradation. This evidence concerns the gene TNFSF11 and rheumatoid arthritis.