Long noncoding RNA XIST regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting miR-9-5p
| Autor: | Chenying Zheng, Xue-Qian Zhao, Jinyu Li, Fan Zhang, Yu-Song Jia, Qin-Sheng Yu, Chunxiao Bai, Shengqian Kang, Qi Sun |
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| Rok vydání: | 2019 |
| Předmět: |
Embryology
Down-Regulation 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Bone Marrow Osteogenesis Gene silencing Humans Osteopontin 3' Untranslated Regions Cells Cultured 030304 developmental biology 0303 health sciences Osteoblasts biology Mesenchymal stem cell ALPL Cell Differentiation Mesenchymal Stem Cells Long non-coding RNA Cell biology Up-Regulation MicroRNAs biology.protein Osteocalcin XIST RNA Long Noncoding 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Mechanisms of development. 162 |
| ISSN: | 1872-6356 |
| Popis: | This study aimed to investigate whether X inactivate-specific transcript (XIST) regulated the expression of tissue non-specific alkaline phosphatase (ALPL) through miR-9-5p to promote osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). We elucidated the molecular regulation mechanisms of XIST underlying osteogenic differentiation of hBMSCs. In osteoporotic patients with hBMSCs, the expression of miR-9-5p was upregulated and the expression of XIST was downregulated. When hBMSCs were treated with osteogenic induction, the expression of XIST was increased and the expression of miR-9-5p was decreased. The osteogenic differentiation of hBMSCs was significantly decreased after knocking down XIST. Luciferase analysis revealed that XIST could directly bind to miR-9-5p and exert a negative regulatory effect on its expression. MiR-9-5p could bind directly to the 3'-UTR of ALPL and inhibit the expression of ALPL. Knockout of XIST reduced the expression of ALPL, while co-transfection of the miR-9-5p inhibitor could reverse the expression of the ALPL gene. In hBMSCs, overexpression of XIST upregulated the expression of ALPL, but the miR-9-5p mimic could reverse the expression of ALPL. Furthermore, silencing of ALPL could downregulate the expression of osteopontin(OPN) and osteocalcin(OCN) induced by miR-9-5p inhibitors. In conclusion, XIST regulated the expression of ALPL by targeting miR-9-5p. It could be used as a positive regulator of osteogenic differentiation of hBMSC. |
| Databáze: | OpenAIRE |
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