O-GlcNAcylation mediates Wnt-stimulated bone formation by rewiring aerobic glycolysis

ABSTRACT: Wnt signaling is an important target for anabolic therapies in osteoporosis. A sclerostin-neutralizing antibody (Scl-Ab), that blocks the Wnt signaling inhibitor (sclerostin), has been shown to promote bone mass in animal models and clinical studies. However, the cellular mechanisms by which Wnt signaling promotes osteogenesis remain to be further investigated. O-GlcNAcylation, a dynamic posttranslational modification of proteins, controls multiple critical biological processes including transcription, translation, and cell fate determination. Here, we report that Wnt3a either induces O-GlcNAcylation rapidly via the Ca2+-PKA-Gfat1 axis, or increases it in a Wnt-β-catenin dependent manner following prolonged stimulation. Importantly, we find O-GlcNAcylation indispensable for osteoblastogene

SUBMITTER: Chengjia You 

PROVIDER: S-SCDT-10_1038-S44319-024-00237-Z | biostudies-other |

REPOSITORIES: biostudies-other