牙龈卟啉单胞菌通过铁超载诱导DNA氧化应激损伤,消耗CTCF表达,阻止牙周韧带干细胞成骨分化。

IF 2.2 4区 生物学 Q3 CELL BIOLOGY
Ying Zhang, Chenchen Si, Changyi Yang, Aijuan Wang, Bohan Yu
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引用次数: 0

摘要

我们旨在研究牙龈卟啉单胞菌(P. gingivalis)对铁超载介导的牙周韧带干细胞(PDLSCs) DNA氧化损伤和成骨分化的影响,特别关注ccctc结合因子(CTCF)的作用。PDLSCs与不同浓度的牙龈假单胞菌来源的LPS共培养。此外,用铁螯合剂去铁胺(DFO)或重组CTCF蛋白共同处理PDLSCs。采用Western blot、免疫荧光染色、流式细胞术和透射电镜(TEM)观察铁超载介导的PDLSCs DNA氧化损伤。根据碱性磷酸酶(ALP)活性、矿化结节形成和骨相关蛋白表达来评估成骨分化。牙周炎患者牙龈组织CTCF水平下调。牙龈P.来源的LPS显著降低了PDLSCs的活力,抑制了CTCF蛋白的表达,特别是在高浓度(1 μg/mL 10 μg/mL)时。然而,与DFO共处理可通过上调CTCF表达、降低细胞内铁水平、脂质过氧化和DNA损伤来减轻这些影响。此外,P. gingivalis来源的LPS通过降低ALP活性、矿化和骨相关蛋白Runx2、BMP2、BMP4、OPN和OCN的表达水平来抑制成骨分化。然而,重组CTCF处理显著逆转了这种抑制作用。我们的研究结果强调了牙龈卟啉菌通过抑制CTCF对PDLSC的有害影响,并强调了DFO和CTCF在保持PDLSC功能和成骨潜能方面的潜在治疗作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Porphyromonas gingivalis induced DNA oxidative stress damage by iron overload to deplete CTCF expression and prevent osteogenic differentiation of periodontal ligament stem cells.

We aimed to investigate the effects of Porphyromonas gingivalis (P. gingivalis) on DNA oxidative damage and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) mediated by iron overload, with special attention to the role of CCCTC-binding factor (CTCF). PDLSCs were co-cultured with different concentrations of P. gingivalis-derived LPS. In addition, deferoxamine (DFO, an iron chelator) or recombinant CTCF protein were used to co-treat PDLSCs. Western blot, immunofluorescence staining, flow cytometry and transmission electron microscopy (TEM) were used to observe the iron overload mediated DNA oxidative damage in PDLSCs. Osteogenic differentiation was assessed based on alkaline phosphatase (ALP) activity, mineralization nodule formation, and bone-related protein expression. CTCF was down-regulated in the gingival tissue of periodontitis patients. P. gingivalis-derived LPS significantly decreased the viability of PDLSCs and suppressed CTCF protein expression, particularly at high concentrations (1 μg/mL 10 μg/mL P. gingivalis-derived LPS). However, co-treatment with DFO alleviated these effects by up-regulating CTCF expression and reducing intracellular iron levels, lipid peroxidation, and DNA damage. Furthermore, P. gingivalis-derived LPS inhibited osteogenic differentiation by decreasing ALP activity, mineralization, and expression levels of bone-associated proteins Runx2, BMP2, BMP4, OPN, and OCN. However, this inhibition was significantly reversed by recombinant CTCF treatment. Our findings underscore the detrimental impact of P. gingivalis on PDLSCs through the suppression of CTCF and highlight the potential therapeutic role of DFO and CTCF in preserving PDLSC function and osteogenic potential.

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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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