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 EMBO Reports, 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).
