Heat stress promotes osteogenic and odontogenic differentiation of stem cells from apical papilla via glucose-regulated protein 78-mediated autophagy

IF 3.1 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of Dental Sciences Pub Date : 2025-01-01 DOI:10.1016/j.jds.2024.05.007

Xiaolan Zhang , Zhou Wei , Yunlong Xu

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Abstract

Background/purpose

Heat stress is essential for improving the efficacy of mesenchymal stem cell (MSC)-based regeneration medicine. However, it is still unclear whether and how heat stress influences the differentiation of stem cells from apical papilla (SCAPs). This research aimed to explore the potential mechanism of glucose-regulated protein 78 (GRP78) in regulating differentiation under heat stress in SCAPs.

Materials and methods

The proliferation ability was assessed using the 5-Ethynyl-2’- deoxyuridine (EdU) assay, cell counting kit assay (CCK-8), and flow cytometry (FCM). The osteogenic and odontogenic differentiation capacities were investigated through Western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), alkaline phosphatase (ALP) staining and activity assay, alizarin red S (ARS) staining, as well as immunofluorescence staining. Western blot and transmission electron microscopy (TEM) were used to detect autophagy.

Results

Heat stress enhanced the osteogenic and odontogenic differentiation of SCAPs, but it did not significantly affect proliferation. Besides, GRP78 has been confirmed to modulate the differentiation induced by heat stress. Autophagy triggered by GRP78 enhanced osteogenic and odontogenic differentiation of SCAPs, while the knockdown of GRP78 or the inhibitor of autophagy suppressed the differentiation.

Conclusion

Heat stress induces osteogenic and odontogenic differentiation of SCAPs through GRP78-mediated autophagy.

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热应激通过葡萄糖调控蛋白 78 介导的自噬作用促进根尖乳头干细胞的成骨和成牙分化

背景/目的热应激是提高间充质干细胞（MSC）再生医学疗效的关键。然而，热应激是否以及如何影响根尖乳头（SCAPs）干细胞的分化尚不清楚。本研究旨在探讨葡萄糖调节蛋白78 （glucse -regulated protein 78, GRP78）在热胁迫下调控SCAPs分化的潜在机制。材料和方法采用5-乙基-2 ' -脱氧尿苷（EdU）法、细胞计数试剂盒（CCK-8）和流式细胞术（FCM）评估细胞增殖能力。采用Western blot、定量逆转录聚合酶链反应（qRT-PCR）、碱性磷酸酶（ALP）染色及活性测定、茜素红S （ARS）染色、免疫荧光染色等方法研究成骨细胞和成牙细胞分化能力。Western blot和透射电镜（TEM）检测细胞自噬。结果应激可促进SCAPs的成骨分化和成牙分化，但对SCAPs的增殖无明显影响。此外，GRP78对热胁迫诱导的分化有调节作用。GRP78引发的自噬增强了SCAPs的成骨和成牙分化，而GRP78的下调或自噬抑制剂抑制了SCAPs的分化。结论热应激通过grp78介导的自噬诱导SCAPs成骨分化和成牙分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Dental Sciences 医学-牙科与口腔外科

CiteScore

5.10

自引率

14.30%

发文量

348

审稿时长

6 days

期刊介绍： he Journal of Dental Sciences (JDS), published quarterly, is the official and open access publication of the Association for Dental Sciences of the Republic of China (ADS-ROC). The precedent journal of the JDS is the Chinese Dental Journal (CDJ) which had already been covered by MEDLINE in 1988. As the CDJ continued to prove its importance in the region, the ADS-ROC decided to move to the international community by publishing an English journal. Hence, the birth of the JDS in 2006. The JDS is indexed in the SCI Expanded since 2008. It is also indexed in Scopus, and EMCare, ScienceDirect, SIIC Data Bases. The topics covered by the JDS include all fields of basic and clinical dentistry. Some manuscripts focusing on the study of certain endemic diseases such as dental caries and periodontal diseases in particular regions of any country as well as oral pre-cancers, oral cancers, and oral submucous fibrosis related to betel nut chewing habit are also considered for publication. Besides, the JDS also publishes articles about the efficacy of a new treatment modality on oral verrucous hyperplasia or early oral squamous cell carcinoma.