Let-7c regulates proliferation and osteodifferentiation of human adipose-derived mesenchymal stem cells under oxidative stress by targeting SCD-1
| Autor: | Jie Tao, Yao Wang, Yunpeng Zhang, Yuanshan Lu, Lin Du, Zihui Zhou |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Bone disease Physiology Osteoporosis Adipose tissue medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Reactive oxygen species formation Osteogenesis microRNA medicine Humans Cells Cultured Osteoporosis Postmenopausal Aged Cell Proliferation Osteoblasts Chemistry Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Cell Biology Middle Aged medicine.disease Cell biology MicroRNAs Oxidative Stress 030104 developmental biology Adipose Tissue Female 030217 neurology & neurosurgery Oxidative stress Stearoyl-CoA Desaturase Bone mass |
| Zdroj: | American journal of physiology. Cell physiology. 316(1) |
| ISSN: | 1522-1563 |
| Popis: | Osteoporosis is a progressive bone disease characterized by decreased bone mass and density, which usually parallels a reduced antioxidative capacity and increased reactive oxygen species formation. Adipose-derived mesenchymal stem cells (ADMSCs), a population of self-renewing multipotent cells, are a well-recognized source of potential bone precursors with significant clinical potential for tissue regeneration. We previously showed that overexpressing stearoyl-CoA desaturase 1 (SCD-1) promotes osteogenic differentiation of mesenchymal stem cells. Micro-RNAs (miRNAs) are noncoding RNAs recently recognized to play key roles in many developmental processes, and miRNA let-7c is downregulated during osteoinduction. We found that let-7c was upregulated in the serum of patients with postmenopausal osteoporosis compared with healthy controls. Levels of let-7c during osteogenic differentiation of ADMSCs were examined under oxidative stress in vitro and found to be upregulated. Overexpression of let-7c inhibited osteogenic differentiation, whereas inhibition of let-7c function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase activity, and matrix mineralization. The luciferase reporter assay was used to validate SCD-1 as a target of let-7c. Further experiments showed that silencing of SCD-1 significantly attenuated the effect of let-7c inhibitor on osteoblast markers, providing strong evidence that let-7c modulates osteogenic differentiation by targeting SCD-1. Inhibition of let-7c promoted the translocation of β-catenin into nuclei, thus activating Wnt/β-catenin signaling. Collectively, these data suggest that let-7c is induced under oxidative stress conditions and in osteoporosis, reducing SCD-1 protein levels, switching off Wnt/β-catenin signaling, and inhibiting osteogenic differentiation. Thus, let-7c may be a potential therapeutic target in the treatment of osteoporosis and especially postmenopausal osteoporosis. |
| Databáze: | OpenAIRE |
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