SIRT7 promotes dental pulp stem cells replicative senescence through desuccinylation of ROCK1

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2024-11-22 DOI:10.1016/j.tice.2024.102636

Rui Zhang , Jie Chen , Yuanyuan Chen , Yangyang Li

{"title":"SIRT7 promotes dental pulp stem cells replicative senescence through desuccinylation of ROCK1","authors":"Rui Zhang , Jie Chen , Yuanyuan Chen , Yangyang Li","doi":"10.1016/j.tice.2024.102636","DOIUrl":null,"url":null,"abstract":"<div><div>The therapeutic effectiveness of dental pulp stem cells (DPSCs) is limited. Sirtuin 7 (SIRT7) has been reported to be associated with a variety of age-related diseases. We aimed to identify the regulatory role of SIRT7 in DPSC senescence and investigate the underlying mechanism. DPSCs were isolated from healthy adults, the stem markers were verified by flow cytomerty analysis. Replicative senescence was induced in DPSCs by serial passage and cells were analyzed at PD16 and 54. DPSC senescence was evaluated by observing senescence-associated β-galactosidase (SA-β-gal) and telomerase reverse transcriptase (TERT) activity. Meanwhile, the markers of senescence levels were monitored by western blotting assay. SIRT7 protein was pulled-down, and the binding relationship between SIRT7 and ROCK1 was verified by immunoprecipitation and western blotting methods. Replicative senescence was induced in DPSCs at PD54. The number of SA-β-gal stained DPSCs significantly increased in the PD54 group while the level of TERT activity was decreased. The cyclin-dependent kinase inhibitors p53, p21, and p16, which are markers of senescence, were markedly up-regulated at PD54. SIRT7 was also found to be lowly expressed at PD54. Inhibition of SIRT7 significantly accelerated the senescence of DPSCs. Moreover, SIRT7 can bind with ROCK1, and SIRT7 could lead to ROCK1 desuccinylation at K520. Inhibited ROCK1 significantly reversed the effects of SIRT7 knockdown on regulating DPSCs senescence. Our results demonstrate that the SIRT7/ROCK1 axis plays a key role in the regulation of DPSC senescence and provide a candidate target to improve the functional and therapeutic potential of DPSCs.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"92 ","pages":"Article 102636"},"PeriodicalIF":2.7000,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816624003379","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The therapeutic effectiveness of dental pulp stem cells (DPSCs) is limited. Sirtuin 7 (SIRT7) has been reported to be associated with a variety of age-related diseases. We aimed to identify the regulatory role of SIRT7 in DPSC senescence and investigate the underlying mechanism. DPSCs were isolated from healthy adults, the stem markers were verified by flow cytomerty analysis. Replicative senescence was induced in DPSCs by serial passage and cells were analyzed at PD16 and 54. DPSC senescence was evaluated by observing senescence-associated β-galactosidase (SA-β-gal) and telomerase reverse transcriptase (TERT) activity. Meanwhile, the markers of senescence levels were monitored by western blotting assay. SIRT7 protein was pulled-down, and the binding relationship between SIRT7 and ROCK1 was verified by immunoprecipitation and western blotting methods. Replicative senescence was induced in DPSCs at PD54. The number of SA-β-gal stained DPSCs significantly increased in the PD54 group while the level of TERT activity was decreased. The cyclin-dependent kinase inhibitors p53, p21, and p16, which are markers of senescence, were markedly up-regulated at PD54. SIRT7 was also found to be lowly expressed at PD54. Inhibition of SIRT7 significantly accelerated the senescence of DPSCs. Moreover, SIRT7 can bind with ROCK1, and SIRT7 could lead to ROCK1 desuccinylation at K520. Inhibited ROCK1 significantly reversed the effects of SIRT7 knockdown on regulating DPSCs senescence. Our results demonstrate that the SIRT7/ROCK1 axis plays a key role in the regulation of DPSC senescence and provide a candidate target to improve the functional and therapeutic potential of DPSCs.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.