TNF and rheumatoid arthritis: 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.