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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
TGF-Beta Induced Key Genes of Osteogenic and Adipogenic Differentiation in Human Mesenchymal Stem Cells and
Genfa Du1, Xinyuan Cheng2, Zhen Zhang1
1Department of Orthopedics, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Shenzhen, China.
Abstract:
Background: The clinical efficacy of osteoporosis therapy is unsatisfactory. However, there is currently no gold standard for the treatment of osteoporosis. Recent studies have indicated that a switch from osteogenic to adipogenic differentiation in human bone marrow mesenchymal stem cells (hMSCs) induces osteoporosis. This study aimed to provide a more comprehensive understanding of the biological mechanisms involved in this process and to identify key genes involved in osteogenic and adipogenic differentiation in hMSCs to provide new insights for the prevention and treatment of osteoporosis. Methods: Microarray and bioinformatics approaches were used to identify the differentially expressed genes (DEGs) involved in osteogenic and adipogenic differentiation, and the biological functions and pathways of these genes were analyzed. Hub genes were identified, and the miRNA-mRNA interaction networks of these hub genes were constructed. Results: In an optimized microenvironment, transforming growth factor-beta (TGF-beta) could promote osteogenic differentiation and inhibit adipogenic differentiation of hMSCs. According to our study, 98 upregulated genes involved in osteogenic differentiation and 66 downregulated genes involved in adipogenic differentiation were identified, and associated biological functions and pathways were analyzed. Based on the protein-protein interaction (PPI) networks, the hub genes of the upregulated genes (CTGF, IGF1, BMP2, MMP13, TGFB3, MMP3, and SERPINE1) and the hub genes of the downregulated genes (PPARG, TIMP3, ANXA1, ADAMTS5, AGTR1, CXCL12, and CEBPA) were identified, and statistical analysis revealed significant differences. In addition, 36 miRNAs derived from the upregulated hub genes were screened, as were 17 miRNAs derived from the downregulated hub genes. Hub miRNAs (hsa-miR-27a/b-3p, hsa-miR-128-3p, hsa-miR-1-3p, hsa-miR-98-5p, and hsa-miR-130b-3p) coregulated both osteogenic and adipogenic differentiation factors. Conclusion: The upregulated hub genes identified are potential targets for osteogenic differentiation in hMSCs, whereas the downregulated hub genes are potential targets for adipogenic differentiation. These hub genes and miRNAs play important roles in adipogenesis and osteogenesis of hMSCs. They may be related to the prevention and treatment not only of osteoporosis but also of obesity.
Insights
This study identifies key genes and miRNAs regulating human bone marrow mesenchymal stem cell differentiation, offering new therapeutic targets for osteoporosis and obesity by understanding the switch between bone formation and fat storage.
Area of Science:
- Biomedical Science
- Molecular Biology
- Stem Cell Research
Background:
- Osteoporosis treatment efficacy is limited, with no established gold standard.
- A shift in human bone marrow mesenchymal stem cells (hMSCs) from osteogenic to adipogenic differentiation is linked to osteoporosis.
- Understanding the molecular mechanisms driving this differentiation switch is crucial for developing new therapies.
Purpose of the Study:
- To elucidate the biological mechanisms underlying the osteogenic and adipogenic differentiation of hMSCs.
- To identify key genes and microRNAs (miRNAs) involved in these differentiation processes.
- To provide novel insights for the prevention and treatment of osteoporosis and potentially obesity.
Main Methods:
- Utilized microarray and bioinformatics analyses to identify differentially expressed genes (DEGs) in hMSCs.
- Constructed protein-protein interaction (PPI) networks to identify hub genes.
- Developed miRNA-mRNA interaction networks to analyze regulatory relationships.
Main Results:
- Identified 98 upregulated genes promoting osteogenesis and 66 downregulated genes promoting adipogenesis.
- Pinpointed key hub genes for osteogenesis (e.g., CTGF, IGF1, BMP2) and adipogenesis (e.g., PPARG, CEBPA).
- Discovered specific miRNAs (e.g., hsa-miR-27a/b-3p, hsa-miR-128-3p) that co-regulate both differentiation pathways.
Conclusions:
- Upregulated hub genes are potential therapeutic targets for promoting osteogenic differentiation.
- Downregulated hub genes may serve as targets for inhibiting adipogenic differentiation.
- Identified hub genes and miRNAs are critical regulators of hMSC differentiation, relevant to osteoporosis and obesity treatment.
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