Progranulin deficiency associates with postmenopausal osteoporosis via increasing ubiquitination of estrogen receptor α.

ABSTRACT: Estrogen deficiency is considered the most important cause of postmenopausal osteoporosis. However, the underlying mechanism is still not completely understood. In this study, progranulin (PGRN) was isolated as a key regulator of bone mineral density in postmenopausal women through high throughput proteomics screening. In addition, PGRN-deficient mice exhibited significantly lower bone mass than their littermates in an ovariectomy-induced osteoporosis model. Furthermore, estrogen-mediated inhibition of osteoclastogenesis and bone resorption as well as its protection against ovariectomy-induced bone loss largely depended on PGRN. Mechanistic studies revealed the existence of a positive feedback regulatory loop between PGRN and estrogen signaling. In addition, loss of PGRN led to the reducti

SUBMITTER: Li G 

PROVIDER: S-EPMC11570241 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature