上海口腔医学

上海口腔医学 ›› 2023, Vol. 32 ›› Issue (6): 583-589.doi: 10.19439/j.sjos.2023.06.005

• 论著 • 上一篇    下一篇

炎症微环境作用下BMP9通过ERK5/KLF4信号通路促进牙周膜干细胞成骨分化

李莉1, 连文伟2,3   

  1. 1.萍乡市第三人民医院 口腔科, 江西 萍乡 337000;
    2.江西省口腔生物医学重点实验室,江西 南昌 330006;
    3.南昌大学附属口腔医院 修复二科,江西 南昌 330006
  • 收稿日期:2023-07-28 修回日期:2023-09-08 出版日期:2023-12-15 发布日期:2024-01-12
  • 通讯作者: 连文伟,E-mail: 656842584@qq.com
  • 作者简介:李莉（1981- ）, 女,硕士, 副主任医师,E-mail: 13979986255@163.com

BMP9 promotes osteogenic differentiation of periodontal ligament stem cells under inflammatory environment via ERK5/KLF4 signaling pathway

LI Li1, LIAN Wen-Wei2,3   

  1. 1. Department of Stomatology, The Third People's Hospital of Pingxiang. Pingxiang 337000;
    2. Jiangxi Provincial Key Laboratory of Stomatological Biomedical Sciences. Nanchang 330006;
    3. Second Department of Prosthetics, Dental Hospital Affiliated to Nanchang University. Nanchang 330006, Jiangxi Province, China
  • Received:2023-07-28 Revised:2023-09-08 Online:2023-12-15 Published:2024-01-12

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摘要： 目的: 探讨骨形态蛋白9（bone morphogenetic protein 9,BMP9）在炎症环境中是否通过ERK5/KLF4信号通路促进牙周膜干细胞（periodontal ligament stem cells,PDLSCs）成骨分化。方法: 利用重组腺病毒技术,在TNF-α刺激的PDLSCs中过表达BMP9,通过RT-PCR和Western 印迹法检测成骨相关基因及蛋白的表达变化。随后,通过转染技术使KLF4在PDLSCs中过表达,在炎症条件下观察其对成骨分化及相关基因表达的效应。在KLF4敲低的背景下过表达BMP9,观察其对成骨分化的影响。添加ERK5抑制剂BIX02189,揭示ERK5在BMP9诱导的成骨分化中的关键作用。采用SPSS 20.0软件包对数据进行统计学分析。结果: BMP9在炎症环境下显著促进PDLSCs成骨分化,并增强KLF4表达。KLF4过表达进一步加强了PDLSCs成骨分化。然而,当KLF4被敲低时,BMP9对PDLSCs成骨促进效应受到明显抑制。BMP9处理显著增加ERK5磷酸化水平,但在ERK5被抑制后,BMP9对成骨分化的促进效应大幅减弱。结论: BMP9可在炎症环境中通过ERK5/KLF4信号通路显著促进PDLSCs成骨分化。

关键词: 骨形态蛋白9, KLF4, 牙周膜干细胞, 成骨分化, 炎症环境, ERK5/KLF4信号通路

Abstract: PURPOSE: To explore how bone morphogenetic protein 9(BMP9) promotes the osteogenic differentiation of periodontal ligament stem cells(PDLSCs) via ERK5/KLF4 signaling pathway under an inflammatory environment. METHODS: Recombinant adenovirus to overexpress BMP9 in PDLSCs stimulated with TNF-α was used and the expression level of osteogenic-related genes and proteins in BMP9-treated cells was examined using RT-PCR and Western blot. Then, KLF4 was overexpressed in PDLSCs via transfection and subjected to inflammatory stimulation to observe its effects on osteogenic differentiation and the expression of osteogenic-related genes. overexpression of BMP9 under the condition of KLF4 knockdown was conducted and its effects on osteogenic differentiation and the expression of osteogenic-related genes was analyzed. ERK5 inhibitor BIX02189 was used to explore the role of ERK5 in BMP9-induced osteogenic differentiation. Statistical analysis was performed with SPSS 20.0 software package. RESULTS: BMP9 could promote the osteogenic differentiation of PDLSCs and the expression of KLF4 in an inflammatory environment. Moreover, the overexpression of KLF4 further promoted the osteogenic differentiation of PDLSCs. However, when KLF4 was knocked down, the osteogenic differentiation promotion effect of BMP9 on PDLSCs was weakened. After BMP9 treatment, the phosphorylation level of ERK5 significantly increased. However, after adding ERK5 inhibitor, the promoting effect of BMP9 on osteogenic differentiation was significantly reduced. CONCLUSIONS: BMP9 can promote the osteogenic differentiation of PDLSCs via ERK5/KLF4 signaling pathway in an inflammatory environment.

Key words: Bone morphogenetic protein 9, Kruppel-like factor 4, Periodontal ligament stem cells, Osteogenic differentiation, Inflammatory environment, ERK5/KLF4 signaling pathway

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