Estrogen Suppresses Osteoclast Function and Cytoskeletal Remodeling via Modulation of the RhoA-Pkn3-c-Src Signaling Pathway in Ovariectomized Rats

Abstract

Simple Summary Postmenopausal osteoporosis is a common skeletal disorder caused mainly by increased bone loss after estrogen decline. Osteoclasts, the cells responsible for bone resorption, become overactive during estrogen deficiency and contribute to osteoporosis progression. Although estrogen is widely used to prevent bone loss, the mechanisms by which it regulates osteoclast function remain incompletely understood. In this study, we found that estrogen reduced osteoclast activity and protected against bone loss in an ovariectomized rat model. Further experiments showed that estrogen inhibited osteoclast formation, bone resorption, and cytoskeletal remodeling by suppressing the RhoA-Pkn3-c-Src signaling pathway. Activation of RhoA provided additional evidence supporting the involvement of this pathway in estrogen-mediated regulation of osteoclast function. These findings provide new insights into how estrogen regulates osteoclast activity and may contribute to the development of improved strategies for preventing estrogen deficiency-related bone loss.