Silencing of miR-483-5p alleviates postmenopausal osteoporosis by targeting SATB2 and PI3K/AKT pathway
| Autor: | Fujiang Zhao, Ting Wan, Zhexu Wen, Guihao Zheng, Guicai Sun, Yulong Ouyang, Yier Xu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Aging
Bone morphogenetic protein 2 Rats Sprague-Dawley postmenopausal osteoporosis Phosphatidylinositol 3-Kinases chemistry.chemical_compound SATB2 Animals Humans Medicine Gene silencing LY294002 Gene Silencing Viability assay Protein kinase B Cells Cultured Osteoporosis Postmenopausal PI3K/AKT/mTOR pathway business.industry Matrix Attachment Region Binding Proteins Cell Biology miR-483-5p PI3K/AKT pathway RUNX2 MicroRNAs Gene Expression Regulation chemistry Cancer research Ovariectomized rat Female business Proto-Oncogene Proteins c-akt Signal Transduction Transcription Factors Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.202552 |
| Popis: | Postmenopausal osteoporosis (PMOP) poses a significant threat to women’s health worldwide. However, detailed molecular mechanism and therapeutic strategy for PMOP remain insufficient. Accumulating evidence suggests that miR-48-5p is implicated in the pathogenesis of osteoporosis. The present study aimed to determine the role and mechanism of miR-483-5p in PMOP. Results from PMOP patients demonstrated that miR-483-5p was up-regulated and SATB2 was down-regulated. Luciferase reporter assay identified SATB2 as a direct target gene of miR-483-5p. Experiments in MC3T3-E1 cells indicated that miR-483-5p mimic markedly inhibited cell viability as well as the expressions of OPG, RUNX2 and BMP2. And miR-483-5p inhibitor, SATB2-overexpressed lentiviruses (Lv-SATB2) or LY294002 (PI3K/AKT inhibitor) significantly reversed the above results. Similarly, PI3K/AKT signaling was activated by miR-483-5p mimic, and was inhibited in miR-483-5p inhibitor, Lv-SATB2 or LY294002 treated cells. In vivo experiments showed that miR-483-5p inhibitor significantly increased the bone mineral density and biomechanical parameters of femurs in ovariectomized (OVX) rats by targeting SATB2. In addition, the osteogenic differentiation and PI3K/AKT signaling were also regulated by miR-483-5p-SATB2 axis. Taken together, our findings indicated that miR-483-5p contributed to the pathogenesis of PMOP by inhibiting SATB2 and activating PI3K/AKT pathway. MiR-483-5p/SATB2 could be selected as a potential therapeutic target for PMOP. |
| Databáze: | OpenAIRE |
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