HSD17B7 Counters Bone Loss in Estrogen Deficiency via Estrogen Receptor Stabilization and Mediates the Effect of Raloxifene.

ABSTRACT: Estrogen receptor (ER) α is a central regulator of osteoclasts in osteoporosis induced by estrogen deficiency. ERα is regulated through interactions with various coactivators; however, the precise mechanisms of these interactions are not yet fully understood. We screened for proteins that bind to ERα using LC-MS/MS and identified a physical interaction between HSD17B7 and ERα, specifically ERα binding to the 119-172 domain of HSD17B7. This interaction blocked ubiquitin-proteasomal degradation of ERα and increased ERE activity. Estrogen-deficient mice lacking HSD17B7 in their preosteoclasts showed more severe bone loss than control mice. This was attributed to increased mitochondrial biogenesis through the activation of PLD1-mTOR signaling. Additionally, in preosteoclasts derived from patie

SUBMITTER: Zhang J 

PROVIDER: S-EPMC12860897 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature