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.
Highlights
Osteoporosis is one of the most common chronic aged-related diseases in the world, and it is especially common in postmenopausal women (Zhi et al, 2021)
To better evaluate the TGF-beta-induced switch from adipogenic to osteogenic differentiation, 24 samples of human bone marrow mesenchymal stem cells (hMSCs) were selected from a BMP2+IBMX (BI) group and a BMP2+IBMX+TGF-beta (BIT) group
The differentially expressed genes (DEGs) from the four time-points were combined, and the overlap of the final 98 upregulated and 66 downregulated genes was visualized as a Venn diagram (Figures 2A,B) and a volcano map (Figure 2C)
Summary
Osteoporosis is one of the most common chronic aged-related diseases in the world, and it is especially common in postmenopausal women (Zhi et al, 2021). It is characterized by loss of bone mass, degeneration of bone microstructure, and reduction of bone strength (Black and Roen, 2016). There is still no gold standard for the treatment of osteoporosis (McClung et al, 2019). 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
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