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Hypoxia‐responsive miRNA‐21‐5p inhibits Runx2 suppression by targeting SMAD7 in MC3T3‐E1 cells
- Source :
- Journal of Cellular Biochemistry
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Sustained hypoxia inhibits osteogenesis and osteoblast differentiation by downregulating the expression of runt‐related transcription factor 2 (Runx2). MicroRNAs (miRNAs) have been shown to regulate osteogenesis and osteoblast differentiation. In the present study, we profiled miRNAs, with microRNA array and quantitative real‐time polymerase chain reaction (RT‐PCR) methods, in mouse osteoblast (MC3T3‐E1) cells under hypoxia. Then, we investigated regulation by miRNA‐21‐5p on the expression of Runx2 and other osteoblast differentiation‐associated markers via gain‐of‐function and loss‐of‐function strategies. We found that expression of miRNA‐21‐5p, miRNA‐210‐5p, and other eight miRNAs was upregulated significantly in hypoxia‐treated MC3T3‐E1 cells. miRNA‐21‐5p overexpression downregulated the expression of the mRNA and protein of suppressor of mothers against decapentaplegic (SMAD7) markedly, the 3′‐untranslated region (3′‐UTR) of which was highly homologous with the miRNA‐21‐5p sequence. miRNA‐21‐5p overexpression upregulated the protein expression of Runx2 in hypoxia‐treated MC3T3‐E1 cells, although mRNA expression of Runx2 and other osteoblast differentiation‐associated molecules (eg, osteocalcin, procollagen type 1 amino‐terminal propeptide, P1NP) were not regulated by it; such upregulation was SMAD7‐dependent. In conclusion, hypoxia‐responsive miRNA‐21‐5p promoted Runx2 expression (at least in part) by targeting the 3′‐UTR and downregulating SMAD7 expression. Our study suggests a protective role of miRNA‐21‐5p in promoting osteoblast differentiation under hypoxia.
- Subjects :
- musculoskeletal diseases
0301 basic medicine
Untranslated region
Osteocalcin
Core Binding Factor Alpha 1 Subunit
Biochemistry
Cell Line
Smad7 Protein
Mice
03 medical and health sciences
SMAD7
0302 clinical medicine
Downregulation and upregulation
Osteogenesis
Runx2
microRNA
medicine
Animals
3' Untranslated Regions
Molecular Biology
Transcription factor
Research Articles
miRNA‐21‐5p
Messenger RNA
Osteoblasts
hypoxia
Chemistry
Osteoblast
3T3 Cells
Cell Biology
Peptide Fragments
Cell biology
RUNX2
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
osteoblast differentiation
030220 oncology & carcinogenesis
Mothers against decapentaplegic
Procollagen
Research Article
Subjects
Details
- ISSN :
- 10974644 and 07302312
- Volume :
- 120
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....5c8edc218515c8217b59b51fdf4078c0