Intracellular glucose starvation inhibits osteogenic differentiation in human periodontal ligament cells
Intracellular glucose starvation inhibits osteogenic differentiation in human periodontal ligament cells
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DOI：
10.1111/jre.13112
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发表时间：
2023-03-08
影响因子：
3.5
通讯作者：
Umeda, Makoto
中科院分区：
文献类型：
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作者：
Deng, Xin;Kato, Hirohito;Umeda, Makoto
背景牙周膜细胞（Periodicalligament cells，PDLCs）是口腔内的间充质细胞，与牙周组织再生密切相关。然而，局部葡萄糖缺乏对牙周组织再生的影响，如术后立即，仍然未知。在本研究中，我们研究了低糖环境对PDLCs增殖和成骨分化的影响。材料和方法我们使用了五种葡萄糖浓度（100，75，50，25和0 mg/dL）的培养基，并专注于低葡萄糖环境对PDLCs增殖，成骨分化和自噬的影响。此外，我们重点关注了低葡萄糖环境中乳酸产生的变化，并研究了乳酸与AZD 3965（一种单羧酸转运蛋白-1（MCT-1）抑制剂）的关系。结果低糖环境抑制PDLCs的增殖、迁移和成骨分化，诱导自噬相关因子LC 3和p62的表达。在低葡萄糖条件下，乳酸和ATP的产生减少。在正常葡萄糖条件下添加AZD 3965（MCT-1抑制剂）导致PDLC出现与低葡萄糖条件下相似的趋势。结论PDLCs成骨分化过程中存在葡萄糖代谢途径产生乳酸。低葡萄糖环境减少乳酸的产生，抑制细胞增殖，迁移和成骨分化，诱导PDLCs的自噬。
BackgroundPeriodontal 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. ObjectiveIn the present study, we investigated the effect of a low-glucose environment on the proliferation and osteogenic differentiation of PDLCs. Materials and MethodsWe 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. ResultsThe 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. ConclusionOur 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.