High Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts
High Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts
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DOI：
10.1902/jop.2015.150474
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发表时间：
2016-04-01
影响因子：
4.3
通讯作者：
Umeda, Makoto
中科院分区：
文献类型：
--
作者：
Kato, Hirohito;Taguchi, Yoichiro;Umeda, Makoto
背景：糖尿病（Diabetes mellitus，DM）是牙周病的一个主要危险因素，影响牙周组织的多种细胞功能。牙周膜干细胞（PDLSCs）在牙周组织再生中发挥重要作用，然而，高血糖对PDLSCs的影响尚不清楚。本研究的目的是探讨高血糖是否影响牙周组织再生，使用人PDLSCs和高糖培养基作为DM的模型。方法：PDLSCs来自健康成人下颌第三磨牙。通过在培养基中培养PDLSC来研究细胞增殖、成骨细胞分化和促炎细胞因子表达，培养基中补充有代表对照患者（5.5 mM）、餐后或控制DM患者（8.0 mM）和未控制DM患者（12.0和24.0 mM）的四种不同葡萄糖浓度。研究了高血糖对PDLSC生理学的分子效应，重点是核因子（NF）-κ B B信号通路。NF-κ B的参与进行了研究与一个特定的NF-κ B抑制剂在PDLSCs hyperglycemic conditions.Results：高糖水平抑制PDLSC增殖和分化为成骨细胞，但诱导NF-κ B激活和随后的白细胞介素（IL）-6和IL-8的表达。治疗与NF-κ B B抑制剂挽救了细胞增殖和成骨细胞分化的缺陷，并抑制IL-6的表达所造成的高糖environment.Conclusion：本研究的结果表明，高血糖抑制人PDLSC增殖和成骨细胞分化。
Background: Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high-glucose medium as a model of DM.Methods: PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)-(kappa B signaling pathway. The involvement of NF-kappa B was investigated with a specific NF-kappa B inhibitor in PDLSCs under hyperglycemic conditions.Results: High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF-kappa B activation and subsequent interleukin (IL)-6 and IL-8 expression. Treatment with an NF-kappa B inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL-6 expression caused by the high-glucose environment.Conclusion: The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation.