FSH enhances the inflammatory response of macrophages in the knee joint possibly through the NFκB pathway.

Previous studies have suggested that women with higher follicle-stimulating hormone (FSH) levels have a greater incidence of osteoarthritis (OA) compared to women with lower FSH despite normal estrogen levels. Our previous studies also showed that FSH has a negative effect on cartilage in postmenopausal OA. However, no studies have investigated the effect of FSH on the synovium. Here, we showed that the FSH receptor (FSHR) is expressed on RAW264.7 cells and BMDM (Bone Marrow-Derived Macrophages), and found that FSH stimulation promotes the production and secretion of inflammatory cytokines in synovial macrophages. In RAW264.7 cells, FSH stimulation enhances phosphorylation and nuclear translocation of P65, suggesting the activation of NFκB signaling, while the knockdown of FSHR eliminates the proinflammatory effect of FSH. To further validate these results, we used an ovariectomy mouse model supplemented with FSH and estrogen, and a mouse model with FSH neutralization. We noted that FSHR was expressed on mouse synovial joint membranes. Furthermore, in ovariectomy mice supplemented with estrogen and treated with FSH, synovial macrophages were significantly increased, while the opposite was the case in the FSH neutralizing group, which suggest that FSH triggers an inflammatory response in the synovial tissue in mice. Taken together, our results indicate that FSH is an important regulator in synovial inflammation via NFκB signaling activation and, to some extent, appears to accelerate the development of osteoarthritis.