文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

FTO 通过 SMOC2 正向调控炎症微环境下牙髓干细胞的成牙本质分化。

FTO Positively Regulates Odontoblastic Differentiation via SMOC2 in Human Stem Cells from the Apical Papilla under Inflammatory Microenvironment.

机构信息

Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.

Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China.

出版信息

Int J Mol Sci. 2024 Apr 5;25(7):4045. doi: 10.3390/ijms25074045.

DOI:10.3390/ijms25074045
PMID:38612855
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11012055/
Abstract

Odontoblastic differentiation of human stem cells from the apical papilla (hSCAPs) is crucial for continued root development and dentin formation in immature teeth with apical periodontitis (AP). Fat mass and obesity-associated protein (FTO) has been reported to regulate bone regeneration and osteogenic differentiation profoundly. However, the effect of FTO on hSCAPs remains unknown. This study aimed to identify the potential function of FTO in hSCAPs' odontoblastic differentiation under normal and inflammatory conditions and to investigate its underlying mechanism preliminarily. Histological staining and micro-computed tomography were used to evaluate root development and FTO expression in SD rats with induced AP. The odontoblastic differentiation ability of hSCAPs was assessed via alkaline phosphatase and alizarin red S staining, qRT-PCR, and Western blotting. Gain- and loss-of-function assays and online bioinformatics tools were conducted to explore the function of FTO and its potential mechanism in modulating hSCAPs differentiation. Significantly downregulated FTO expression and root developmental defects were observed in rats with AP. FTO expression notably increased during in vitro odontoblastic differentiation of hSCAPs, while lipopolysaccharide (LPS) inhibited FTO expression and odontoblastic differentiation. Knockdown of FTO impaired odontoblastic differentiation, whereas FTO overexpression alleviated the inhibitory effects of LPS on differentiation. Furthermore, FTO promoted the expression of secreted modular calcium-binding protein 2 (SMOC2), and the knockdown of SMOC2 in hSCAPs partially attenuated the promotion of odontoblastic differentiation mediated by FTO overexpression under LPS-induced inflammation. This study revealed that FTO positively regulates the odontoblastic differentiation ability of hSCAPs by promoting SMOC2 expression. Furthermore, LPS-induced inflammation compromises the odontoblastic differentiation of hSCAPs by downregulating FTO, highlighting the promising role of FTO in regulating hSCAPs differentiation under the inflammatory microenvironment.

摘要

人根尖乳头干细胞（hSCAPs）的成牙本质分化对于根尖周炎（AP）未成熟牙齿的持续牙根发育和牙本质形成至关重要。脂肪量和肥胖相关蛋白（FTO）已被报道可显著调节骨再生和成骨分化。然而，FTO 对 hSCAPs 的影响尚不清楚。本研究旨在鉴定 FTO 在 hSCAPs 在正常和炎症条件下成牙本质分化中的潜在功能，并初步探讨其潜在机制。组织学染色和微计算机断层扫描用于评估诱导 AP 的 SD 大鼠的牙根发育和 FTO 表达。通过碱性磷酸酶和茜素红 S 染色、qRT-PCR 和 Western blot 评估 hSCAPs 的成牙本质分化能力。通过 gain- 和 loss-of-function 测定和在线生物信息学工具探讨 FTO 的功能及其在调节 hSCAPs 分化中的潜在机制。AP 大鼠中观察到 FTO 表达下调和牙根发育缺陷。体外 hSCAPs 成牙本质分化过程中 FTO 表达明显增加，而脂多糖（LPS）抑制 FTO 表达和牙本质分化。FTO 敲低抑制牙本质分化，而过表达 FTO 则减轻 LPS 对分化的抑制作用。此外，FTO 促进分泌模块钙结合蛋白 2（SMOC2）的表达，而在 LPS 诱导的炎症下，SMOC2 在 hSCAPs 中的敲低部分减弱了 FTO 过表达介导的成牙本质分化的促进作用。本研究表明，FTO 通过促进 SMOC2 表达正向调节 hSCAPs 的成牙本质分化能力。此外，LPS 诱导的炎症通过下调 FTO 来损害 hSCAPs 的成牙本质分化，突出了 FTO 在调节炎症微环境下 hSCAPs 分化中的有前景的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/f0e1193f157c/ijms-25-04045-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/2076e9d2c88d/ijms-25-04045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/fb692ac94f28/ijms-25-04045-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/030d089023e6/ijms-25-04045-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/0888b16bd5ae/ijms-25-04045-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/224374854a4b/ijms-25-04045-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/f0e1193f157c/ijms-25-04045-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/2076e9d2c88d/ijms-25-04045-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/fb692ac94f28/ijms-25-04045-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/030d089023e6/ijms-25-04045-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/0888b16bd5ae/ijms-25-04045-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/224374854a4b/ijms-25-04045-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b4d/11012055/f0e1193f157c/ijms-25-04045-g006.jpg

相似文献

[1]
FTO Positively Regulates Odontoblastic Differentiation via SMOC2 in Human Stem Cells from the Apical Papilla under Inflammatory Microenvironment.

Int J Mol Sci. 2024-4-5

[2]
MiR-199a-5P promotes osteogenic differentiation of human stem cells from apical papilla targeting IFIT2 in apical periodontitis.

Front Immunol. 2023

[3]
NOTUM plays a bidirectionally modulatory role in the odontoblastic differentiation of human stem cells from the apical papilla through the WNT/β-catenin signaling pathway.

Arch Oral Biol. 2024-4

[4]
The N6-methyladenosine demethylase FTO is required for odontoblast differentiation in vitro and dentine formation in mice by promoting RUNX2 exon 5 inclusion through RBM4.

Int Endod J. 2023-12

[5]
The bioceramic sealer iRoot SP promotes osteogenic differentiation of human stem cells from apical papilla via miR-141-3p/SPAG9/MAPK signalling pathway.

Int Endod J. 2023-10

[6]
Differential expression of circular RNAs in interleukin 6-promoted osteogenic differentiation of human stem cells from apical papilla.

Clin Oral Investig. 2023-12

[7]
Effects of iRoot SP on osteogenic differentiation of human stem cells from apical papilla.

BMC Oral Health. 2021-8-18

[8]
Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N-methyladenosine modification of sclerostin.

J Transl Med. 2023-11-4

[9]
Nuclear factor I-C expression pattern in developing teeth and its important role in odontogenic differentiation of human molar stem cells from the apical papilla.

Eur J Oral Sci. 2014-12

[10]
The effects of melatonin on the viability and osteogenic/odontogenic differentiation of human stem cells from the apical papilla.

Mol Biol Rep. 2023-11

引用本文的文献

[1]
Abamectin Causes Neurotoxicity in Zebrafish Embryos.

Int J Mol Sci. 2025-1-3

本文引用的文献

[1]
Fat mass and obesity-associated protein (FTO) affects midpalatal suture bone remodeling during rapid maxillary expansion.

Eur J Orthod. 2024-4-1

[2]
Biological properties of stem cells from the apical papilla exposed to lipopolysaccharides: An in vitro study.

Arch Oral Biol. 2024-3

[3]
Epitranscriptomic modifications in mesenchymal stem cell differentiation: advances, mechanistic insights, and beyond.

Cell Death Differ. 2024-1

[4]
SMOC2 promoted vascular smooth muscle cell proliferation, migration, and extracellular matrix degradation by activating BMP/TGF-β1 signaling pathway.

J Clin Biochem Nutr. 2023-9

[5]
The N6-methyladenosine demethylase FTO is required for odontoblast differentiation in vitro and dentine formation in mice by promoting RUNX2 exon 5 inclusion through RBM4.

Int Endod J. 2023-12

[6]
Stem Cells from the Apical Papilla (SCAPs): Past, Present, Prospects, and Challenges.

Biomedicines. 2023-7-20

[7]
Histologic and Electron Microscopic Characterization of a Human Immature Permanent Premolar with Chronic Apical Abscess 16 Years after Regenerative Endodontic Procedures.

J Endod. 2023-8

[8]
Hereditary dentin defects with systemic diseases.

Oral Dis. 2023-9

[9]
Clinical and radiographic outcomes of regenerative endodontic procedures for traumatized permanent necrotic teeth with apical periodontitis and external root resorption.

Int Endod J. 2023-7

[10]
SMOC2 promotes aggressive behavior of fibroblast-like synoviocytes in rheumatoid arthritis through transcriptional and post-transcriptional regulating MYO1C.

Cell Death Dis. 2022-12-13

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索