Knockdown of human-specific lncRNA MEK6-AS1 improves osteogenic differentiation of senescent mesenchymal stem cells
10.16352/j.issn.1001-6325.2025.05.0568
- VernacularTitle:敲降人组织特异性lncRNA MEK6-AS1改善衰老间充质干细胞成骨分化能力
- Author:
Yunhua CHEN
1
;
Di LI
;
Xiaoyan ZHAO
;
Ming CHEN
;
Hongling LI
;
Chunhua ZHAO
Author Information
1. 中国医学科学院基础医学研究所 北京协和医学院基础学院 组织工程研究中心,北京 100005
- Keywords:
mesenchymal stem cells(MSCs);
senescence;
osteogenic differentiation;
long noncoding RNA(lncRNA);
MEK6-AS1
- From:
Basic & Clinical Medicine
2025;45(5):568-574
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of a novel human-specific long noncoding RNA(lncRNA),MEK6-AS1,and its potential molecular mechanism in improving the osteogenic differentiation of senescent mesenchymal stem cells(MSCs).Methods An in vitro human MSCs replicative senescence model was established by sequen-tial passaging,and then senescence was identified by β staining and senescence-related gene expression.RT-qPCR was used to detect the expression of MEK6-AS1 during senescence and osteogenic differentiation of human MSCs(hMSCs);Lentiviral knockdown technology was used to regulate the expression of MEK6-AS1 in the MSCs replicative senescence model.Transcriptome sequencing technology was utilized to analyze the effects of MEK6-AS1 on the transcriptome of hMSCs especially on genes and pathways related to osteogenic differentiation.The effect of MEK6-AS1 as an intervention target at osteogenic differentiation of human senescent hMSCs was evaluated with alkaline phosphatase staining microscopy.PCR technology was used to detect osteogenic gene expression levels in cells.Results With aging process,the osteogenic differentiation ability of hMSCs decreased significantly while the expression level of MEK6-AS1 was enhanced(P＜0.000 1).Knockdown of MEK6-AS1 significantly enhanced the osteogenic differentiation of MSCs by the up-regulating expression of osteogenic markers and increasing minerali-zation capacity(P＜0.001).Conclusions Knockdown of human-specific lncRNA MEK6-AS1 improves osteogenic differentiation of senescent MSCs,providing a new target and theoretical basis for the treatment of senescence-asso-ciated osteoporosis.
