Lactate from glucose metabolism regulates osteogenic differentiation of human periodontal ligament stem cells

Objectives: Periodontal ligament stem cells (PDLSCs), as one of mesenchymal stem cells in the oral cavity, are closely associated with periodontal hard tissue regeneration. However, the effect of local tissue glucose deficiency on periodontal tissue regeneration, such as immediately after surgical operation, is still unknown. Therefore, this study sought to investigate the effect of a low-glucose environment on the proliferation and osteogenic differentiation of PDLSCs. Material: and methods: This study used medium at five glucose concentrations (100, 75, 50, 25 and 0 mg/dL) and focused on the effects on PDLSCs of changes in lactate in the low-glucose environment. Lactate uptake by PDLSCs in a standard glucose environment was suppressed by the addition of AZD3965, a monocarboxylate transporter-1 inhibitor. Results: : We investigated cell proliferation, migration and assessed osteogenic differentiation factors. Furthermore, PDLSC lactate production was suppressed under low-glucose conditions. We compared that condition to the low-glucose environment to assess lactate's effect on the proliferation and osteogenic differentiation of PDLSCs. The low-glucose environment decreased PDLSC lactate production and inhibited PDLSC osteogenic differentiation. In low glucose environment, the phosphorylation of extracellular signal-regulated kinase, protein kinase B, and the activation of hypoxia-inducible factor 1α signaling pathways were inhibited, also, AZD3965 inhibited the activation of these signaling pathways. Conclusion: The results of this study suggested that lactate production by glucose metabolism is involved in periodontal tissue regeneration. Clinical relevance: The findings of close relationship about lactate metabolism in periodontal tissue may contribute new insights into future periodontal regenerative therapies. Lactate may be a new treatment option for periodontal regenerative therapy in the future.