Pregnane X receptor protects against age-related bone loss in males via PI3K/Akt-mediated inhibition of apoptosis.

ABSTRACT: The pregnane X receptor (Pxr) regulates metabolism and inflammation, but its roles in bone homeostasis remain elusive. This study demonstrates that Pxr deficiency in bones induces osteoporotic phenotypes, with reduced trabecular bone mass, impaired osteogenesis, increased inflammation, and apoptosis. RNA sequencing reveals downregulation of the PI3K/Akt signaling pathway in Pxr-deficient bones, a key pathway linked to cell survival and differentiation. In vitro, primary bone marrow mesenchymal stem cells (BMSCs) with Pxr deficiency exhibited inhibited antioxidant enzyme activity, elevated intracellular reactive oxygen species level, activated pro-inflammatory cytokines, suppressed PI3K/Akt pathway, enhanced apoptosis, and decreased osteogenic differentiation. Conversely, Pxr overexpression

SUBMITTER: Li S 

PROVIDER: S-EPMC12594874 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature