O-GlcNAcylation in the osteoblast lineage-boosting the complexity of Wnt-stimulated bone formation.

Although differentiation and activity of bone-forming osteoblasts are regulated at various levels, there is ample evidence that components of the Wnt signaling pathway play a dominant role in bone mass acquisition. Moreover, a neutralizing antibody blocking the Wnt signaling inhibitor sclerostin has recently been established as a novel osteoanabolic treatment option for osteoporotic patients. Importantly, however, the molecular mechanisms explaining the osteogenic influence of Wnt molecules are still not fully clarified. In this issue of , You and co-workers show that O-GlcNAcylation is required for the osteoanabolic effect of Wnt stimulation, in vitro and in vivo (You et al, 2024).