Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway

doi:10.1093/stmcls/sxae047

科研成果详情

题名	Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway
作者	Lu Chen 1; Xiping Wang 2; Sha Tian 3; Linxi Zhou 4; Li Wang2; Xiaohan Liu 1; Zihan Yang2; Guiqiang Fu 5; Xingguang Liu 6; Chen Ding 3; Duohong Zou 1,2
发表日期	2024-08-22
发表期刊	Stem cells (Dayton, Ohio) 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	HDPSCs ILK cellular senescence osteogenesis proteomic
其他关键词	DNA-DAMAGE ; AUTOPHAGY
摘要	Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affect the dental stromal tissue homeostasis and impair the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated β-galactosidase (SA-β-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mTOR signaling pathway (ILK, MAPK3, mTOR, STAT1 and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-β-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.
资助项目	National Natural Science Foundation of China [32171347]; Foundation of Leading Talents from Shanghai Health Commission [2022XD038]; CAMS Innovation Fund for Medical Sciences [2019-I2M-5-037]; Training Programme for Research Physicians in Innovation and Transformation from shanghai hospital development center [SHDC2022CRD002]; Human Phenome Data Center of Fudan university
出版者	OXFORD UNIV PRESS
ISSN	1066-5099
EISSN	1549-4918
卷号	42 期号:10 页码:861-873
DOI	10.1093/stmcls/sxae047
页数	13
WOS类目	Cell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Oncology ; Cell Biology ; Hematology
WOS研究方向	Cell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
WOS记录号	WOS:001302569800001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	39169713
SCOPUSEID	2-s2.0-85206019538
通讯作者地址	[Zou, Duohong]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Coll Stomatol, Dept Oral Surg,Sch Med, Shanghai 200011, Peoples R China. ; [Zou, Duohong]Natl Clin Res Ctr Oral Dis, Shanghai Key Lab Stomatol, Shanghai 200011, Peoples R China. ; [Zou, Duohong]Shanghai Res Inst Stomatol, Shanghai 200011, Peoples R China. ; [Ding, Chen]Fudan Univ, Human Phenome Inst, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
Scopus学科分类	Medicine (all)
SCOPUS_ID	SCOPUS_ID:85206019538
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/217647
专题	口腔医学院、附属口腔医院口腔医学院、附属口腔医院_口腔医学研究所
作者单位	1.Department of Oral Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai 200011, China.; 2.Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.; 3.State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai 200433, China.; 4.Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, China.; 5.Stomatology Hospital and College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei, China.; 6.National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, 200433, China.
推荐引用方式 GB/T 7714	Lu Chen,Xiping Wang,Sha Tian,et al. Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway[J]. Stem cells (Dayton, Ohio),2024,42(10):861-873.
APA	Lu Chen., Xiping Wang., Sha Tian., Linxi Zhou., Li Wang., ... & Duohong Zou. (2024). Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway. Stem cells (Dayton, Ohio), 42(10), 861-873.
MLA	Lu Chen,et al."Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway".Stem cells (Dayton, Ohio) 42.10(2024):861-873.