2. Academic Validation
  3. FTO/RUNX2 signaling axis promotes cementoblast differentiation under normal and inflammatory condition

FTO/RUNX2 signaling axis promotes cementoblast differentiation under normal and inflammatory condition

  • Biochim Biophys Acta Mol Cell Res. 2022 Dec;1869(12):119358. doi: 10.1016/j.bbamcr.2022.119358.
Qiao Sun 1,  Tingting Zhao 1,  Biao Li 1,  Mengying Li 1,  Ping Luo 1,  Chen Zhang 2,  Gang Chen 3,  Zhengguo Cao 4,  Yicun Li 5,  Mingyuan Du 6,  Hong He 7
Affiliations

Affiliations

  • 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 2 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Orthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 3 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 4 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 5 Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong province, China.
  • 6 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: dumydent@whu.edu.cn.
  • 7 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Orthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: drhehong@whu.edu.cn.
PMID: 36084732 DOI: 10.1016/j.bbamcr.2022.119358
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.

Keywords

Cell differentiation; Cementoblast; Fat mass and obesity-associated protein; Inflammation; N(6)-methyladenosine; Transcription factors.

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