The targeting of YAP by kaempferol regulates bone homeostasis and improves osteoporosis in rats

This study investigated the potential therapeutic effect of kaempferol on osteoporosis by regulating bone homeostasis through the YAP. The ovariectomy model was constructed. The changes in bone and liver tissue were observed through HE staining. Bone metabolism and inflammatory markers were quantitatively analyzed using RT-qPCR and ELISA. Changes in the YAP/NF-κB signaling pathway were detected through Western blot and immunofluorescence. In vitro, the activity and secretion levels of MC3 T3-E1-differentiated osteoblasts were assessed using CCK- 8 and ELISA. The effects of osteoblast-secreted factors on osteoclast-induced differentiation were analyzed using alizarin red staining, phalloidin staining, ELISA, TRAP staining, and SEM. Finally, the regulatory effects of kaempferol on the expression of bone homeostasis in osteoclasts were examined by immunofluorescence and Western blot. Kaempferol treatment improved trabecular bone structure, increased bone density, and modulated bone metabolism by enhancing OPG expression and suppressing TRAP, NFATC1, and RANKL levels. Kaempferol inhibited the activation of the NF-κB pathway and increased YAP expression, reducing inflammatory factors. In vitro, kaempferol promoted osteoblast differentiation and inhibited osteoclast activity. These effects were most pronounced at higher kaempferol doses and were associated with improved bone remodeling and reduced bone resorption. Kaempferol exhibits significant potential for osteoporosis treatment by regulating bone homeostasis, mitigating inflammation through modulating the YAP.