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AP2a enhanced the osteogenic differentiation of mesenchymal stem cells by inhibiting the formation of YAP/RUNX2 complex and BARX1 transcription
- Source :
- Cell Proliferation
- Publication Year :
- 2018
- Publisher :
- John Wiley and Sons Inc., 2018.
-
Abstract
- Objectives Bone regeneration by bone tissue engineering is a therapeutic option for bone defects. Improving the osteogenic differentiation of mesenchymal stem cells (MSCs) is essential for successful bone regeneration. We previously showed that AP2a enhances the osteogenic differentiation in MSCs. The present study investigated the mechanism of how AP2a regulates the direct differentiation. Materials and methods Co‐immunoprecipitation and ChIP assays were carried out to investigate the underlying mechanism in MSCs differentiation. The osteogenic differentiation potential was determined by mineralization ability and the expression of osteogenic marker in vitro and the in vivo bone‐like tissue generation in nude mice. Results We show that AP2a can compete with RUNX2, a key transcription factor in osteogenic differentiation, to recruit YAP and release the inhibition of RUNX2 activity from YAP by forming YAP‐AP2a protein complex. YAP‐AP2a protein complex also interacts with the BARX1 promoter through AP2a, inhibit the transcription of BARX1. Moreover, BARX1 inhibits osteogenic differentiation of MSCs. Conclusions Our discoveries revealed that AP2a may regulate the osteogenic differentiation in an indirect way through competing with RUNX2 to relieve the RUNX2 activity which inhibited by YAP, and also in a direct way via targeting the BARX1 and directly repressed its transcription. Thus, our discoveries shed new light on the mechanism of direct differentiation of MSCs and provide candidate targets for improving the osteogenic differentiation and enhancing bone tissue regeneration.
- Subjects :
- 0301 basic medicine
Calcium Phosphates
Bone Regeneration
Transcription, Genetic
Cell Cycle Proteins
Core Binding Factor Alpha 1 Subunit
Bone tissue
Mice
0302 clinical medicine
Transcription (biology)
Osteogenesis
RNA, Small Interfering
Mice, Inbred BALB C
Chemistry
Nuclear Proteins
General Medicine
yes‐associated protein
Cell biology
RUNX2
medicine.anatomical_structure
030220 oncology & carcinogenesis
Original Article
Female
RNA Interference
Adaptor Protein Complex 2
osteogenic differentiation
Mice, Nude
BARX1
Cell Line
03 medical and health sciences
Adaptor Protein Complex alpha Subunits
In vivo
medicine
AP2a
Animals
Humans
Bone regeneration
Transcription factor
Homeodomain Proteins
mesenchymal stem cells
Tissue Engineering
Mesenchymal stem cell
Cell Biology
Original Articles
In vitro
030104 developmental biology
Durapatite
HEK293 Cells
Gene Expression Regulation
Tooth
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 13652184 and 09607722
- Volume :
- 52
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell Proliferation
- Accession number :
- edsair.doi.dedup.....0b68d20cf39bc7a081f1c3c3cafa4ce3