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Effects of miR-146a on the osteogenesis of adipose-derived mesenchymal stem cells and bone regeneration
- Source :
- Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Increasing evidence has indicated that bone morphogenetic protein 2 (BMP2) coordinates with microRNAs (miRNAs) to form intracellular networks regulating mesenchymal stem cells (MSCs) osteogenesis. This study aimed to identify specific miRNAs in rat adipose-derived mesenchymal stem cells (ADSCs) during BMP2-induced osteogenesis, we selected the most significantly down-regulated miRNA, miR-146a, to systematically investigate its role in regulating osteogenesis and bone regeneration. Overexpressing miR-146a notably repressed ADSC osteogenesis, whereas knocking down miR-146a greatly promoted this process. Drosophila mothers against decapentaplegic protein 4 (SMAD4), an important co-activator in the BMP signaling pathway, was miR-146a’s direct target and miR-146a exerted its repressive effect on SMAD4 through interacting with 3′-untranslated region (3′-UTR) of SMAD4 mRNA. Furthermore, knocking down SMAD4 attenuated the ability of miR-146a inhibitor to promote ADSC osteogenesis. Next, transduced ADSCs were incorporated with poly(sebacoyl diglyceride) (PSeD) porous scaffolds for repairing critical-sized cranial defect, the treatment of miR-146a inhibitor greatly enhanced ADSC-mediated bone regeneration with higher expression levels of SMAD4, Runt-related transcription factor 2 (Runx2) and Osterix in newly formed bone. In summary, our study showed that miR-146a negatively regulates the osteogenesis and bone regeneration from ADSCs both in vitro and in vivo.
- Subjects :
- 0301 basic medicine
Bone Regeneration
Cellular differentiation
Bone Morphogenetic Protein 2
Down-Regulation
Bone morphogenetic protein 2
Article
03 medical and health sciences
0302 clinical medicine
Osteogenesis
Animals
Bone regeneration
BMP signaling pathway
Cells, Cultured
Stem cell transplantation for articular cartilage repair
Oligonucleotide Array Sequence Analysis
Smad4 Protein
Multidisciplinary
Chemistry
Sequence Analysis, RNA
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
Cell biology
Rats
RUNX2
MicroRNAs
030104 developmental biology
Adipose Tissue
030220 oncology & carcinogenesis
Mothers against decapentaplegic
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....9c46e7e9587ba67d5fdd31d980290185