Dataset Information

Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy.

ABSTRACT: BACKGROUND:The differentiation of bone mesenchymal stem cells (BMSCs) into adipogenesis (AD) rather than osteogenesis (OS) is an important pathological feature of osteoporosis. Illuminating the detailed mechanisms of the differentiation of BMSCs into OS and AD would contribute to the interpretation of osteoporosis pathology. METHODS:To identify the regulated mechanism in lineage commitment of the BMSCs into OS and AD in the early stages, the gene expression profiles with temporal series were downloaded to reveal the distinct fates when BMSCs adopt a committed lineage. For both OS and AD lineages, the profiles of days 2-4 were compared with day 0 to screen the differentially expressed genes (DEGs), respectively. Next, the functional enrichment analysis was utilized to find out the biological function, and protein-protein interaction network to predict the central genes. Finally, experiments were performed to verify our finding. RESULTS:FoxO signaling pathway with central genes like FoxO3, IL6, and CAT is the crucial mechanism of OS, while Rap1 signaling pathway of VEGFA and FGF2 enrichment is more significant for AD. Besides, PI3K-Akt signaling pathway might serve as the latent mechanism about the initiation of differentiation of BMSCs into multiple lineages. CONCLUSION:Above hub genes and early-responder signaling pathways control osteogenic and adipogenic fates of BMSCs, which maybe mechanistic models clarifying the changes of bone metabolism in the clinical progress of osteoporosis. The findings provide a crucial reference for the prevention and therapy of osteoporosis.

SUBMITTER: Wu J

PROVIDER: S-EPMC7510089 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy.

Wu Jianjun J Cai Peian P Lu Zhenhui Z Zhang Zhi Z He Xixi X Zhu Bikang B Zheng Li L Zhao Jinmin J

Journal of orthopaedic surgery and research 20200923 1

<h4>Background</h4>The differentiation of bone mesenchymal stem cells (BMSCs) into adipogenesis (AD) rather than osteogenesis (OS) is an important pathological feature of osteoporosis. Illuminating the detailed mechanisms of the differentiation of BMSCs into OS and AD would contribute to the interpretation of osteoporosis pathology.<h4>Methods</h4>To identify the regulated mechanism in lineage commitment of the BMSCs into OS and AD in the early stages, the gene expression profiles with temporal ...[more]

PMID: 32967719

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Project description:BackgroundAs one of the most common chronic diseases in the world, osteoporosis occurs especially in postmenopausal women. Circular RNAs (circRNAs) are emerging as major drivers in human disease. The aim of the present study was to analyse circRNA expression profiles in osteoporosis and to explore the clinical significance and the regulatory molecular mechanism of hsa_circ_0006859 during osteoporosis.MethodsExosomes were isolated from clinically collected serum samples. A circRNA microarray was performed to screen differentially expressed circRNAs. Quantitative real-time PCR (qRT-PCR) and western blot were performed to analyse target gene mRNA expression and protein expression. Alizarin red staining (ARS) was performed to evaluate the mineralization ability of human bone marrow mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to evaluate the lipid droplet formation ability of hBMSCs. Bioinformatics analysis and the luciferase reporter assay were performed to investigate the interaction between two genes.ResultsHsa_circ_0006859 was identified as one of the most upregulated circRNAs in the microarray analysis. Hsa_circ_0006859 in exosomes was upregulated in osteoporosis patients compared to healthy controls. Hsa_circ_0006859 differentiated osteopenia or osteoporosis patients from healthy controls with high sensitivity and specificity. Hsa_circ_0006859 suppressed osteoblastic differentiation and promoted adipogenic differentiation of hBMSCs. Hsa_circ_0006859 directly bound to miR-431-5p, and ROCK1 was identified as a novel target gene of miR-431-5p. Hsa_circ_0006859 is a competing endogenous RNA (ceRNA) of miR-431-5p that promotes ROCK1 expression. Hsa_circ_0006859 suppressed osteogenesis and promoted adipogenesis by sponging miR-431-5p to upregulate ROCK1.ConclusionsExosomal hsa_circ_0006859 is a potential biomarker for postmenopausal osteoporosis and controls the balance between osteogenesis and adipogenesis in hBMSCs by sponging miR-431-5p.

Project description: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.

Dataset Information

Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy.

Publications

Identification of potential specific biomarkers and key signaling pathways between osteogenic and adipogenic differentiation of hBMSCs for osteoporosis therapy.

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