Intracellular glucose starvation inhibits osteogenic differentiation in human periodontal ligament cells

• Published in: Journal of periodontal research Vol. 58; no. 3; pp. 607 - 620
• Main Authors: Deng, Xin, Kato, Hirohito, Taguchi, Yoichiro, Nakata, Takaya, Umeda, Makoto
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2023
• Subjects: Autophagy; Carrier Proteins - metabolism; Cell Differentiation; Cell migration; Cell Proliferation; Cells, Cultured; Glucose; Glucose metabolism; Humans; lactate; Lactates - metabolism; Lactates - pharmacology; Lactic acid; Ligaments; Mesenchyme; Oral cavity; Osteogenesis; osteogenic differentiation; Periodontal Ligament; periodontal ligament cells; Tissue engineering; periodontal ligament cells; lactate; glucose metabolism; osteogenic differentiation
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/jre.13112

Background 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. Objective In the present study, we investigated the effect of a low‐glucose environment on the proliferation and osteogenic differentiation of PDLCs. Materials and Methods 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. Results 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. Conclusion 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.