FTO/RUNX2 signaling axis promotes cementoblast differentiation under normal and inflammatory condition.
Biochim Biophys Acta Mol Cell Res
; 1869(12): 119358, 2022 Dec.
Article
in En
| MEDLINE
| ID: mdl-36084732
ABSTRACT
N6-methyladenosine (m6A) is the most prevalent mRNA modification which plays crucial roles in various biological processes, but its role in cementogenesis remains largely unknown. Here, using time-series transcriptomic analysis, we reveal that mRNA m6A demethylase Fat mass and obesity-associated protein (FTO) is involved in cementogenesis. Knocking down FTO decreases cementoblast differentiation and mineralization in both OCCM-30 cellular model and murine ectopic bone formation model. Mechanistically, we find that FTO directly binds Runt-related transcription factor 2 (Runx2) mRNA, an important cementogenesis factor, thus protecting it from YTH domain-containing family protein 2 (YTHDF2) mediated degradation, when cementoblasts are differentiating. Knocking down YTHDF2 restores the expression of Runx2 in FTO-knockdown cells. Moreover, under inflammatory conditions, TNF-α inhibits cementoblast differentiation and mineralization partly through FTO/RUNX2 axis. Collectively, our study reveals an important regulatory role of FTO/RUNX2 axis in normal and pathological cementogenesis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biological Phenomena
/
Core Binding Factor Alpha 1 Subunit
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biochim Biophys Acta Mol Cell Res
Year:
2022
Document type:
Article
Affiliation country:
China