JARID1B抑制人牙周韧带间充质细胞的成骨潜能。

IF 2.9 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Oral diseases Pub Date : 2024-09-01 Epub Date: 2023-11-22 DOI:10.1111/odi.14814
Rogério S Ferreira, Rodrigo A da Silva, Geórgia Da S Feltran, Ericka Patricia da Silva, Rahyza I F de Assis, Emanuel Silva Rovai, Willian F Zambuzzi, Denise C Andia
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引用次数: 0

摘要

背景:在这里,我们通过考虑牙周韧带细胞成骨分化的异质性来评估组蛋白赖氨酸去甲基化酶5B (JARID1B)是否参与牙周韧带细胞(pdlc)的成骨表型承诺。材料和方法:采用低(l)和高(h)成骨潜能的pdlc作为生物模型,在体外进行成骨刺激的第3天和第10天,通过全基因组DNA(羟基)甲基化、mRNA表达和western blotting分析,研究了参与成骨的一组基因的表观遗传学、转录和蛋白质水平。结果:与l- pdlc相比,h- pdlc显示JARID1B水平降低,RUNX2和RUNX2/p57之间呈显著的反比相关。表观遗传学上,仅在h- pdlc中观察到整体H3K4me3含量的显著降低。免疫印迹数据显示,仅在h- pdlc中,在诱导3天后,H3K4me3的总含量显著降低,而在10天后,两种pdlc中均观察到H3K4me3的总含量增加。此外,全球H3K4me3水平与JARID1B基因表达呈正相关。总之,我们的研究结果显示JARID1B在抑制pdlc成骨表型中的关键作用,这声称临床前方案提出JARID1B作为潜在的治疗靶点。
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JARID1B represses the osteogenic potential of human periodontal ligament mesenchymal cells.

Background: Here, we evaluated whether the histone lysine demethylase 5B (JARID1B), is involved in osteogenic phenotype commitment of periodontal ligament cells (PDLCs), by considering their heterogeneity for osteoblast differentiation.

Materials and methods: Epigenetic, transcriptional, and protein levels of a gene set, involved in the osteogenesis, were investigated by performing genome-wide DNA (hydroxy)methylation, mRNA expression, and western blotting analysis at basal (without osteogenic induction), and at the 3rd and 10th days of osteogenic stimulus, in vitro, using PDLCs with low (l) and high (h) osteogenic potential as biological models.

Results: h-PDLCs showed reduced levels of JARID1B, compared to l-PDLCs, with significant inversely proportional correlations between RUNX2 and RUNX2/p57. Epigenetically, a significant reduction in the global H3K4me3 content was observed only in h-PDLCs. Immunoblotting data reveal a significant reduction in the global H3K4me3 content, at 3 days of induction only in h-PDLCs, while an increase in the global H3K4me3 content was observed at 10 days for both PDLCs. Additionally, positive correlations were found between global H3K4me3 levels and JARID1B gene expression.

Conclusions: Altogether, our results show the crucial role of JARID1B in repressing PDLCs osteogenic phenotype and this claims to pre-clinical protocols proposing JARID1B as a potential therapeutic target.

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来源期刊
Oral diseases
Oral diseases 医学-牙科与口腔外科
CiteScore
7.60
自引率
5.30%
发文量
325
审稿时长
4-8 weeks
期刊介绍: Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.
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