Kato Hirohito, Taguchi Yoichiro, Tominaga Kazuya, Kimura Daisuke, Yamawaki Isao, Noguchi Masahiro, Yamauchi Nobuhiro, Tamura Isao, Tanaka Akio, Umeda Makoto
Department of Periodontology, Osaka Dental University, Osaka, Japan.
Department of Oral Pathology, Osaka Dental University.
J Periodontol. 2016 Apr;87(4):e44-51. doi: 10.1902/jop.2015.150474. Epub 2015 Nov 5.
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.
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)-(κB signaling pathway. The involvement of NF-κB was investigated with a specific NF-κB inhibitor in PDLSCs under hyperglycemic conditions.
High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF-κB activation and subsequent interleukin (IL)-6 and IL-8 expression. Treatment with an NF-κB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL-6 expression caused by the high-glucose environment.
The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation.
糖尿病（DM）是牙周疾病的主要危险因素，会影响多种细胞功能。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。本研究旨在以人PDLSCs和高糖培养基作为糖尿病模型，探讨高血糖是否会影响牙周组织再生。
从健康成年人类下颌第三磨牙获取PDLSCs。通过在补充有代表对照患者（5.5 mM）、餐后或血糖控制的糖尿病患者（8.0 mM）以及血糖未控制的糖尿病患者（12.0和24.0 mM）的四种不同葡萄糖浓度的培养基中培养PDLSCs，研究细胞增殖、成骨细胞分化和促炎细胞因子表达。重点关注核因子（NF）-κB信号通路，研究高血糖对PDLSC生理学的分子影响。在高血糖条件下，用特异性NF-κB抑制剂研究PDLSCs中NF-κB的参与情况。
高糖水平抑制PDLSCs增殖和成骨细胞分化，但诱导NF-κB激活及随后的白细胞介素（IL）-6和IL-8表达。用NF-κB抑制剂处理可挽救细胞增殖和成骨细胞分化缺陷，并抑制高糖环境引起的IL-6表达。
本研究结果表明，高血糖抑制人PDLSCs增殖和成骨细胞分化。
