scholarly journals The p53/miR-145a Axis Promotes Cellular Senescence and Inhibits Osteogenic Differentiation by Targeting Cbfb in Mesenchymal Stem Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Chao Xia ◽  
Tianyuan Jiang ◽  
Yonghui Wang ◽  
Xiaoting Chen ◽  
Yan Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Cellular Senescence ◽  
Negative Regulator ◽  
The Novel ◽  
Binding Factor ◽  
Marrow Mesenchymal Stem Cells ◽  
Core Binding Factor Beta

The osteogenic differentiation capacity of senescent bone marrow mesenchymal stem cells (MSCs) is reduced. p53 not only regulates cellular senescence but also functions as a negative regulator in bone formation. However, the role of p53 in MSCs senescence and differentiation has not been extensively explored. In the present study, we investigated the molecular mechanism of p53 in MSCs senescence and osteogenic differentiation. We found that p53 was upregulated during cellular senescence and osteogenic differentiation of MSCs respectively induced by H2O2 and BMP9. Similarly, the expression of p53-induced miR-145a was increased significantly. Furthermore, Overexpression of miR-145a in MSCs promoted cellular senescence and inhibited osteogenic differentiation. Then, we identified that p53-induced miR-145a inhibited osteogenic differentiation by targeting core binding factor beta (Cbfb), and the restoration of Cbfb expression rescued the inhibitory effects of miRNA-145a. In summary, our results indicate that p53/miR-145a axis exert its functions both in promoting senescence and inhibiting osteogenesis of MSCs, and the novel p53/miR-145a/Cbfb axis in osteogenic differentiation of MSCs may represent new targets in the treatment of osteoporosis.

scholarly journals The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

2020 ◽  
Author(s):  
Chao Xia ◽  
Tianyuan Jiang ◽  
Yonghui Wang ◽  
Xiaoting Chen ◽  
Yan Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Cellular Senescence ◽  
Negative Regulator ◽  
Luciferase Reporter ◽  
Bone Marrow Mscs ◽  
Expression Change ◽  
Core Binding Factor Beta

Abstract Background: The osteogenic differentiation capacity of senescent bone marrow mesenchymal stem cells (MSCs) is diminished. However, little is known about the mechanisms. p53 not only regulates cellular senescence but also, as a negative regulator, is involved in bone formation. This study investigated the molecular mechanism of p53 in cellular senescence and osteogenesis.Methods: The expression of p53 and its downstream gene p21 were measured during cellular senescence and osteogenesis differentiation of primary bone marrow MSCs. Then miR-145a was picked out from those p53-induced miRNAs as its expression change in bone marrow MSCs senescence and osteogenesis induced by H2O2 and BMP-9, respectively. The function of p53 induced miR-145a was analyzed by transfected with miRNA mimic in osteogenic differentiation of MSCs. Western blot and luciferase reporter assay were used for validating the target of miR-145a. Results: p53, its downstream effector p21, and p53-induced miR-145a were significantly upregulated during primary MSCs senescence and osteogenesis. Overexpression of miR-145a promoted cellular senescence and inhibited osteogenic differentiation of MSCs. p53-induced miR-145a inhibited osteogenic differentiation by targeting core binding factor beta (Cbfb), and the restoration of Cbfb expression rescued the inhibitory effects of miRNA-145a on osteogenesis.Conclusions: p53-induced miR-145a functions both in promoting senescence and inhibiting osteogenesis of MSCs, and the novel pathway p53/miR-145a/Cbfb in osteogenic differentiation of MSCs may represent new targets in the treatment of osteoporosis.

scholarly journals Role of nanoparticles in osteogenic differentiation of bone marrow mesenchymal stem cells

2019 ◽  
Vol 72 (1) ◽  
pp. 1-22 ◽  
Author(s):  
Nadia S. Mahmoud ◽  
Hanaa H. Ahmed ◽  
Mohamed R. Mohamed ◽  
Khalda S. Amr ◽  
Hadeer A. Aglan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Marrow Mesenchymal Stem Cells

scholarly journals lncRNA NEAT1 regulates CYP1A2 and influences steroid-induced necrosis

2021 ◽  
Vol 16 (1) ◽  
pp. 969-980
Author(s):  
Yongfang Zhou ◽  
Fei Zhang ◽  
Fengyang Xu ◽  
Qiang Wang ◽  
Jianhua Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Control Group ◽  
Marrow Mesenchymal Stem Cells ◽  
Necrosis Of Femoral Head ◽  
Lncrna Neat1

Abstract The main cause of steroid-induced necrosis of femoral head (SNFH) is excessive glucocorticoid (GC) intake. The aim of this article was to investigate the role of lncRNA NEAT1 as a molecular sponge to adsorb miR-23b-3p and regulate CYP1A2 in SNFH. Fluorescence in situ hybridization was used to localize lncRNA NEAT1. Human bone marrow mesenchymal stem cells (hBMSCs) were collected from patients with SNFH. The expression of lncRNA NEAT1, miR-23b-3p and CYP1A2 in hBMSCs were intervened. Compared to the control group, the lncRNA NEAT1 and CYP1A2 expression in the SNFH group was increased, while miR-23b-3p expression was decreased. GCs could inhibit the osteogenic differentiation of hBMSCs and upregulate the expression of lncRNA NEAT1. Knockdown of lncRNA NEAT1 could promote the proliferation and osteogenic differentiation of hBMSCs in the SNFH group. Overexpression of miR-23b-3p could partially counteract the effect of lncRNA NEAT1 on hBMSCs. CYP1A2 was confirmed to be a target of miR-23b-3p. Overexpression of CYP1A2 could partially rescue the effect of miR-23b-3p overexpression on hBMSCs. In conclusion, lncRNA NEAT1 as a ceRNA can adsorb miR-23b-3p and promote the expression of CYP1A2, which then inhibits the osteogenic differentiation of hBMSCs and promotes the progress of SNFH.

Exosomes from bone marrow mesenchymal stem cells promoted osteogenic differentiation by delivering miR-196a that targeted Dkk1 to activate Wnt/β-catenin pathway

2020 ◽  
Author(s):  
Zhi Peng ◽  
Zhenkai Lou ◽  
Zhongjie Li ◽  
Shaobo Li ◽  
Kaishun Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Osteogenic Differentiation ◽  
Osteoblast Differentiation ◽  
Negative Regulator ◽  
Luciferase Assay ◽  
Alizarin Red ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Osteoporosis is the most common bone metabolic disease. Emerging evidence suggests that exosomes are secreted by diverse cells such as bone marrow mesenchymal stem cells (BMSCs), and play important role in cell-to-cell communication and tissue homeostasis. Recently, the discovery of exosomes has attracted attention in the field of bone remodeling. Methods: The exosomes were extracted from BMSCs and labeled by PKH-67, and then incubated with hFOB1.19 cells to investigate the miR-196a function on the osteoblast differentiation of hFOB1.19. The osteoblast differentiation was detected via alizarin red staining and the expression of osteoblast genes were detected by western blot. The cell apoptosis was detected by flow cytometer. The target relationship of miR-196a and Dickkopf-1 (Dkk1) were verified by luciferase assay and western blot. Results: Here we demonstrated that exosomes extracted from BMSCs (BMSC-exo) significantly promoted hFOB1.19 differentiation to osteoblasts. We found that BMSC-exo were enriched with miR-196a and delivered miR-196a to hFOB1.19 cells to inhibit its target Dkk1, which is a negative regulator of Wnt/β-catenin pathway. Conclusion: BMSC-exo activated Wnt/β-catenin pathway to promote osteogenic differentiation, while BMSC-exo failed to exert the effects when miR-196a was deprived. In conclusion, miR-196a delivered by exosomes from BMSCs plays an essential role in enhancing osteoblastic differentiation by targeting Dkk1 to activate Wnt/β-catenin pathway.

scholarly journals The Critical Role of Long Noncoding RNA in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoling Qiu ◽  
Bo Jia ◽  
Xiang Sun ◽  
Weitao Hu ◽  
Hongxing Chu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Critical Role ◽  
Human Bone ◽  
Differentially Expressed ◽  
Human Bone Marrow ◽  
Marrow Mesenchymal Stem Cells

Objective. Long noncoding RNAs (lncRNAs) have been demonstrated to regulate many biological processes including differentiation. However, their role in osteogenic differentiation was poorly known. Materials and Methods. In this study, we first globally profiled the differentially expressed lncRNAs and mRNAs during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs). Bioinformatics analysis was performed to further analyze these significantly changed molecules. Then the role of lncRNA ENST00000502125.2 in the osteogenic differentiation was determined. Results. A number of lncRNAs and mRNAs were significantly differentially expressed during hBMMSC osteogenic differentiation. Among them, 433 lncRNAs and 956 mRNAs were continuously upregulated, while 232 lncRNAs and 229 mRNAs were continuously downregulated. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that carbohydrate derivative binding and complement and coagulation cascades were most correlated molecular function and pathway, respectively. Downregulation of lncRNA ENST00000502125.2 promoted the osteogenic differentiation of hBMMSCs, and opposite results were found when lncRNA ENST00000502125.2 was upregulated. Conclusions. lncRNAs play a critical role in the osteogenic differentiation of hBMMSCs and targeting lncRNA ENST00000502125.2 might be a promising strategy to promote osteogenic differentiation.

Sign in / Sign up

Export Citation Format

Share Document