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CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin α5 expression
- Source :
- Cell Death and Differentiation
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group UK, 2020.
-
Abstract
- Adipose-derived mesenchymal stem cells (ADSCs) are promising candidate for regenerative medicine to repair non-healing bone defects due to their high and easy availability. However, the limited osteogenic differentiation potential greatly hinders the clinical application of ADSCs in bone repair. Accumulating evidences demonstrate that circular RNAs (circRNAs) are involved in stem/progenitor cell fate determination, but their specific role in stem/progenitor cell osteogenesis, remains mostly undescribed. Here, we show that circRNA-vgll3 originating from the vgll3 locus markedly enhances osteogenic differentiation of ADSCs; nevertheless, silencing of circRNA-vgll3 dramatically attenuates ADSC osteogenesis. Furthermore, we validate that circRNA-vgll3 functions in ADSC osteogenesis through a circRNA-vgll3/miR-326-5p/integrin α5 (Itga5) pathway. Itga5 promotes ADSC osteogenic differentiation and miR-326-5p suppresses Itga5 translation. CircRNA-vgll3 directly sequesters miR-326-5p in the cytoplasm and inhibits its activity to promote osteogenic differentiation. Moreover, the therapeutic potential of circRNA-vgll3-modified ADSCs with calcium phosphate cement (CPC) scaffolds was systematically evaluated in a critical-sized defect model in rats. Our results demonstrate that circRNA-vgll3 markedly enhances new bone formation with upregulated bone mineral density, bone volume/tissue volume, trabeculae number, and increased new bone generation. This study reveals the important role of circRNA-vgll3 during new bone biogenesis. Thus, circRNA-vgll3 engineered ADSCs may be effective potential therapeutic targets for bone regenerative medicine.
- Subjects :
- Male
Adipose tissue
Bone healing
Integrin alpha5
Regenerative medicine
Article
Rats, Sprague-Dawley
Osteogenesis
microRNA
Gene silencing
Animals
RNA-Seq
Progenitor cell
Molecular Biology
Cells, Cultured
Bone mineral
Chemistry
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
Cell Biology
RNA, Circular
Cell biology
Stem-cell research
Rats
MicroRNAs
Adipose Tissue
Epigenetics
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 14765403 and 13509047
- Volume :
- 28
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell Death and Differentiation
- Accession number :
- edsair.doi.dedup.....ffe226f80e3ad41dff95354512224a75