Abstract |
Osteoporosis results from the imbalance between osteogenesis and bone resorption mediated by osteoblasts and osteoclasts. During the disease process of osteoporosis, the alteration of gene expression occurs, which lead to the disease progression. MicroRNAs ( miRNAs) have been previously demonstrated to be modulators for bone metabolism via regulation of osteoblast and osteoclast differentiation. In the present study, we detected the expression levels of five osteoporosis-related miRNAs in bone and serum samples of patient with or without osteoporosis. The downstream molecular mechanism of miR-363-3p was analyzed and detected by using bioinformatics analysis and mechanism experiment. The upstream transcription factor of miR-363-3p was analyzed by applying bioinformatics analysis and ChIP assay and luciferase reporter assay. The role of this pathway in osteoclastogenesis was demonstrated by functional assays. MiR-363-3p was significantly highly expressed in osteoporotic samples. Mechanistically, miR-363-3p promotes osteoclastogenesis and inhibits osteogenic differentiation by targeting PTEN and therefore activating PI3K/AKT signaling pathway. MiR-363-3p was activated by its upstream transcription activator MYB. This study revealed that MYB-induced upregulation of miR-363-3p regulates osteoporosis pathogenesis via PTEN/PI3K/AKT signaling pathway.
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Authors | Mingyi Li, Ruolan Luo, Wenjian Yang, Zhen Zhou, Chenxia Li |
Journal | In vitro cellular & developmental biology. Animal
(In Vitro Cell Dev Biol Anim)
Vol. 55
Issue 5
Pg. 376-386
(May 2019)
ISSN: 1543-706X [Electronic] Germany |
PMID | 31025251
(Publication Type: Journal Article)
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Chemical References |
- MIRN363 microRNA, human
- MYB protein, human
- MicroRNAs
- Proto-Oncogene Proteins c-myb
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- PTEN Phosphohydrolase
- PTEN protein, human
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Topics |
- Bone Resorption
(blood, genetics, pathology)
- Bone and Bones
(metabolism, pathology)
- Cell Differentiation
(genetics)
- Computational Biology
- Gene Expression Regulation
(genetics)
- Humans
- MicroRNAs
(blood, genetics)
- Osteoblasts
(metabolism, pathology)
- Osteoclasts
(metabolism, pathology)
- Osteogenesis
(genetics)
- Osteoporosis
(blood, genetics, pathology)
- PTEN Phosphohydrolase
(genetics)
- Patients
- Phosphatidylinositol 3-Kinases
(genetics)
- Proto-Oncogene Proteins c-akt
(genetics)
- Proto-Oncogene Proteins c-myb
(genetics)
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