Intracellular glucose starvation inhibits osteogenic differentiation in human periodontal ligament cells

Periodontal ligament cells (PDLCs), as mesenchymal cells in the oral cavity, are closely linked to periodontal tissue regeneration. However, the effect of local glucose deficiency on periodontal tissue regeneration, such as immediately post-surgery, remains unknown.In the present study, we investigated the effect of a low-glucose environment on the proliferation and osteogenic differentiation of PDLCs.We used media with five glucose concentrations (100, 75, 50, 25, and 0 mg/dL) and focused on the effects of a low-glucose environment on the proliferation, osteogenic differentiation, and autophagy of PDLCs. Additionally, we focused on changes in lactate production in a low-glucose environment and investigated the involvement of lactate with AZD3965, a monocarboxylate transporter-1 (MCT-1) inhibitor.The low-glucose environment inhibited PDLCs proliferation, migration, and osteogenic differentiation, and induced the expression of the autophagy-related factors LC3 and p62. Lactate and ATP production were decreased under low-glucose conditions. The addition of AZD3965 (MCT-1 inhibitor) in normal glucose conditions caused a similar trend as in low-glucose conditions on PDLCs.Our results suggest lactate production through glucose metabolism in the osteogenic differentiation of PDLCs. A low-glucose environment decreased lactate production, inhibiting cell proliferation, migration, and osteogenic differentiation and inducing autophagy in PDLCs.