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Published on: May 4, 2018
YTHDC2 inhibits rat bone mesenchymal stem cells osteogenic differentiation by accelerating RUNX2 mRNA degradation via
Bo Ma1,2, Pei Cao3,4, Lichen Zhang2
1Department of Trauma and Orthopedics, Peking University People's Hospital, Beijing, PR China.
Abstract:
As the most abundant internal mRNA modification, N6-methyladenosine (m6A) RNA methylation has been found to influence many biological events including bone mesenchymal stem cells (BMSCs) osteogenic differentiation. YTH N6-methyladenosine RNA binding protein C2 （YTHDC2） is an m6A reading protein with the ability to mediate the decay of combined methylated mRNA, however its role in BMSCs osteogenic differentiation remains unknown. In this study, we first found an increase of RUNX family transcription factor 2 （RUNX2） expression and a decrease of YTHDC2 expression during the process of BMSCs osteogenic differentiation. Furthermore, we transfected BMSCs with YTHDC2 interference fragment, resulting in an increased content of RUNX2 mRNA and protein inside BMSCs. Finally, through RNA Immunoprecipitation experiments, we confirmed that YTHDC2 protein can bind to RUNX2 mRNA and accelerate its decomposition. Moreover, the immunofluorescence staining also showed a negative correlation between YTHDC2 and RUNX2. In conclusion, during BMSCs osteogenic differentiation, YTHDC2 protein showed decreased expression, resulting in a higher level of RUNX2 (mRNA and protein) expression inside cells, indicating YTHDC2 as a promising molecular target for the regulation of BMSCs osteogenic differentiation.
Insights
YTHDC2 expression decreases during bone mesenchymal stem cell (BMSC) osteogenic differentiation, leading to increased RUNX2 levels. This suggests YTHDC2 is a key regulator in BMSC differentiation.
Area of Science:
- Molecular Biology
- Stem Cell Biology
- Epigenetics
Background:
- N6-methyladenosine (m6A) RNA methylation is a crucial epigenetic modification impacting gene expression.
- Bone mesenchymal stem cells (BMSCs) differentiate into osteoblasts, a process vital for bone formation and repair.
- YTHDC2 is an m6A reader protein involved in mRNA decay, but its role in BMSC osteogenesis is unexplored.
Purpose of the Study:
- To investigate the role of YTHDC2 in the osteogenic differentiation of BMSCs.
- To determine the relationship between YTHDC2, RUNX2, and BMSC differentiation.
Main Methods:
- Quantitative analysis of YTHDC2 and RUNX2 expression during BMSC osteogenic differentiation.
- Transfection of BMSCs with YTHDC2 interference fragments.
- RNA Immunoprecipitation (RIP) assays.
- Immunofluorescence staining.
Main Results:
- YTHDC2 expression decreased, while RUNX2 expression increased during BMSC osteogenic differentiation.
- YTHDC2 knockdown led to elevated RUNX2 mRNA and protein levels.
- YTHDC2 directly binds to RUNX2 mRNA, promoting its degradation.
- A negative correlation was observed between YTHDC2 and RUNX2 expression.
Conclusions:
- YTHDC2 negatively regulates RUNX2 expression during BMSC osteogenic differentiation.
- Decreased YTHDC2 expression contributes to increased RUNX2 levels, promoting osteogenesis.
- YTHDC2 represents a potential therapeutic target for modulating BMSC differentiation and bone formation.
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