[P1-2-01] Effect of histone modification by lactate on osteoblast differentiation
Keywords:lactylation、osteoblasts differentiation、p300
Lactate is a metabolite produced by lactate dehydrogenase (LDH)A in the glycolytic system. Recently, a novel modification of histones by lactate, lactylation, was found to be involved in transcriptional regulation. We have reported that intracellular lactate concentration is important for osteoblast differentiation. In this study, we aim to elucidate a new mechanism of osteoblast differentiation via histone lactylation other than energy metabolism and oxidative effects by lactate. Differentiation of osteoblast-like cells was assessed using ALP activity staining and Real-time PCR. Histone lactylation was evaluated by westernblot. C2C12 cells cultured in high-glucose medium increased osteoblast differentiation and histone lactylation compared to those in low-glucose medium. The addition of lactate to low-glucose medium also restored osteoblast differentiation and histone lactylation. Furthermore, osteoblast differentiation and histone lactylation were decreased stimulated with the LDH inhibitor (oxamate) or induced p300 siRNA in C2C12 cells. These results suggest that gene regulation by histone lactylation plays an important role in promoting osteoblast differentiation in undifferentiated cells and that regulation of lactate production may be a new target for the treatment of bone metabolism diseases.