Evaluating the effect of LPS from periodontal pathogenic bacteria on the expression of senescence-related genes in human dental pulp stem cells

被引:8
作者
Sattari, Mandana [1 ]
Masoudnia, Mina [1 ]
Mashayekhi, Kazem [2 ]
Hashemi, Seyed Mahmoud [1 ]
Khannazer, Nikoo [1 ]
Sattari, Sepanta [1 ]
Haftcheshmeh, Saeed Mohammadian [3 ]
Momtazi-Borojeni, Amir Abbas [3 ]
机构
[1] Shahid Beheshti Univ Med Sci, Fac Med, Dept Immunol, Tehran, Iran
[2] Rafsanjan Univ Med Sci, Res Inst Basic Med Sci, Immunol Infect Dis Res Ctr, Rafsanjan, Iran
[3] Neyshabur Univ Med Sci, Noncommunicable Dis Res Ctr, Neyshabur, Iran
关键词
CDKN1A; CDKN2A; DPSCs; LPS; senescence; SIRT1; TP53; CELLULAR SENESCENCE; REPLICATIVE SENESCENCE; P21(WAF1/CIP1/SDI1); STIMULATION; ACTIVATION; PROMOTES; ROLES;
D O I
10.1111/jcmm.17594
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The human dental pulp stem cells (hDPSCs) are one of the readily available sources of multipotent mesenchymal stem cells (MSCs) and can be considered as a type of tool cells for cell-based therapies. However, the main limitation in the clinical use of these cells is DPSC senescence, which can be induced by lipopolysaccharide (LPS) of oral pathogenic bacteria. Up to now, far little attention has been paid to exploring the molecular mechanisms of senescence in DPSCs. So, the current study aimed to investigate the underlying molecular mechanism of senescence in hDPSCs stimulated with Porphyromonas gingivalis (P. gingivalis) and Escherichia coli (E. coli)-derived LPSs, by evaluating both mRNA and protein expression of four important senescence-related genes, including TP53, CDKN1A, CDKN2A and SIRT1. To this purpose, hDPSCs were stimulated with different LPSs for 6, 24 and 48 h and then the gene expression was evaluated using quantitative real-time polymerase chain reaction (qPCR) and western blotting. Following stimulation with P. gingivalis and E. coli-derived LPSs, the relative mRNA and protein expression of all genes were significantly up-regulated in a time-dependent manner, as compared with unstimulated hDPSCs. Moreover, the hDPSCs stimulated with P. gingivalis LPS for 6 and 24 h had the highest mRNA expression of CDKN1A and SIRT1, respectively (p < 0.0001), whereas the highest mRNA expression of CDKN2A and TP53 was seen in hDPSCs stimulated with E. coli LPS for 48 h (p < 0.0001). In summary, because DPSCs have been reported to have therapeutic potential for several cell-based therapies, targeting molecular mechanisms aiming at preventing DPSC senescence could be considered a valuable strategy.
引用
收藏
页码:5647 / 5656
页数:10
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