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

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 post-translational 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-ß-catenin-dependent manner following prolonged stimulation. Importantly, we find O-GlcNAcylation indispensable for osteoblastogenesis both in vivo and in vitro. Genetic ablation of O-GlcNAcylation in the osteoblast-lineage diminishes bone formation and delays bone fracture healing in response to Wnt stimulation in vivo. Mechanistically, Wnt3a induces O-GlcNAcylation at Serine 174 of PDK1 to stabilize the protein, resulting in increased glycolysis and osteogenesis. These findings highlight O-GlcNAcylation as an important mechanism regulating Wnt-induced glucose metabolism and bone anabolism.

Are you really smiling? Display rules for emojis and the relationship between emotion management and psychological well-being.

Display rules specify socially appropriate facial expressions in a given situation. However, managing emotions for such a social adaption sometimes leads to deleterious psychological outcomes. Given that people nowadays rely on emojis to express emotions online, the present study investigated (1) whether display rules exist in emoji communications and (2) how emotion management using emojis is associated with psychological well-being. Prior studies have demonstrated the effects of context on the frequency of emoji use. However, the intensity and type of expression may differ, even if emojis are used at the same frequency. The current study thus investigated whether emotional expressions and the types of emojis used are adjusted to contexts similar to facial displays. As many as 1,289 Japanese participants typed emojis in response to Internet chats and reported the intensity of their emotional expressions. The contexts of the chats varied depending on the target of use, the emotional value of contexts, and private or public settings. The results showed that, similar to facial displays, individuals expressed emotions through emojis more with those closely related, more in positive contexts than in negative contexts, and more in private than in public contexts. When the expressions were intense, individuals used emojis consistent with the emotional value of the context. Upon attenuating the expressions, this study found that individuals tended to use euphemistic emojis and sent smiling emojis in negative contexts to manage the expressions. Moreover, expressing emotions with emojis was associated with subjective well-being, whereas managing emotions with emojis was weakly associated with depressive symptoms. Together, this study indicates the existence of display rules for emojis, calling for future research on the psychological impact of online emotion norms.