scholarly journals Dynamics of Transcription Factors in Three Early Phases of Osteogenic, Adipogenic, and Chondrogenic Differentiation Determining the Fate of Bone Marrow Mesenchymal Stem Cells in Rats

Author(s):  
Qingyu Zhang ◽  
Jun Dong ◽  
Peng Zhang ◽  
Dongsheng Zhou ◽  
Fanxiao Liu

The imbalance of osteogenic, adipogenic, and chondrogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) occurred in multiple age-related degenerative diseases such as osteoporosis and osteoarthritis. In order to improve our understanding and control of multi-directional differentiation of BMSCs in rats, using high-throughput sequencing, we identified key gene regulatory events in the early stages of lineage commitment. Data analysis revealed two transcription factors (TFs, Tsc22d3, and Epas1) with elevated expression throughout the initiation of differentiation (3 h), lineage acquisition (12 h), and early lineage progression (72 h) of three-directional differentiation. For osteogenic differentiation, 792, 1,042, and 638 differentially expressed genes including 48, 59, and 34 TFs were identified at three time points, respectively. Moreover, the functional analysis demonstrated that 4, 12, and 5 TFs were only differentially expressed during osteogenic differentiation at 3, 12, and 72 h, respectively, and not during other two-directional differentiation. Hopx showed enhanced expression throughout three early phases during the osteogenic differentiation but no significant change in other two-directional differentiation. A similar pattern of Gbx2 expression occurred in chondrogenic differentiation. Thus, Hopx and other early responder TFs may control the osteogenic cell fate of BMSCs and participate in the development of osteoporosis. Gbx2 and other early responder TFs should be considered in mechanistic models that clarify cartilage-anabolic changes in the clinical progression of osteoarthritis.

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoling Qiu ◽  
Bo Jia ◽  
Xiang Sun ◽  
Weitao Hu ◽  
Hongxing Chu ◽  
...  

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Xiang Sun ◽  
Junchuan Cao ◽  
Jiusong Han ◽  
Bo Jia ◽  
Jing Wang ◽  
...  

Objective. This study is aimed at investigating the role of long noncoding RNA (lncRNA) RP11-815M8.1 in the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Methods. RT-PCR was used to detect the expression of lncRNA RP11-815M8.1 before and after osteogenic differentiation of hBMSCs. The lncRNA RP11-815M8.1 in hBMSCs was overexpressed or silenced via lentiviral transfection. The transfection efficiency was detected by RT-PCR, and the proliferation of hBMSCs was determined by CCK-8. After 14 days of osteogenic differentiation of transfected hBMSCs, the expression of osteogenic transcription factors (ALP, OCN, OPN, Runx2, and Osterix) was detected by alizarin red staining and RT-PCR. The mRNAs directly regulated by lncRNA RP11-815M8.1 and targeted miRNAs were analyzed according to the positional relationship between lncRNA and mRNA in the genome and miRanda software. Results. The expression of lncRNA RP11-815M8.1 enhanced with increasing osteogenic differentiation time of hBMSCs. Two days after the transfection of hBMSCs, lncRNA RP11-815M8.1 expression was significantly increased in the overexpression group and significantly decreased in the knockdown group, compared to control cells. The CCK-8 assay showed that overexpression and knockdown of lncRNA RP11-815M8.1 did not affect the proliferation of hBMSCs. After 14 days of differentiation of hBMSCs, stronger alizarin red staining was observed in the overexpression groups, and the expression of osteogenic transcription factors was increased in the overexpression group compared to the control. In the knockdown group, alizarin red staining and the expression of osteogenic transcription factors were decreased. Bioinformatics analysis showed that lncRNA RP11-815M8.1 was directly associated with one mRNA, 27 interacting miRNAs, and 20 miRNA-targeted mRNAs. Conclusion. The osteogenic differentiation of hBMSCs can be promoted by lncRNA RP11-815M8.1 in vitro.


2021 ◽  
Author(s):  
Xia Yi ◽  
Ping Wu ◽  
Jianyun Liu ◽  
Shan He ◽  
Ying Gong ◽  
...  

Adipogenesis and osteoblastogenesis (adipo-osteoblastogenesis) are closely related processes involving with the phosphorylation of numerous cytoplasmic proteins and key transcription factors.


2014 ◽  
Vol 2 (23) ◽  
pp. 3609-3617 ◽  
Author(s):  
Haifeng Zeng ◽  
Xiyu Li ◽  
Fang Xie ◽  
Li Teng ◽  
Haifeng Chen

A novel approach for labelling and tracking BMSCs in bone tissue engineering by using dextran-coated fluorapatite nanorods doped with lanthanides.


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