Abstract | BACKGROUND:
Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. METHODS: RESULTS: Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. CONCLUSIONS: AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes.
|
Authors | Jie Zhou, Yanlin Zhu, Dongqing Ai, Mengjiao Zhou, Han Li, Guangyue Li, Leilei Zheng, Jinlin Song |
Journal | Journal of translational medicine
(J Transl Med)
Vol. 21
Issue 1
Pg. 781
(11 04 2023)
ISSN: 1479-5876 [Electronic] England |
PMID | 37925419
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2023. The Author(s). |
Chemical References |
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO
- FTO protein, human
- Glycation End Products, Advanced
- N-methyladenosine
- RNA
- SOST protein, human
- Adaptor Proteins, Signal Transducing
|
Topics |
- Humans
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO
(genetics)
- Bone Marrow Cells
(metabolism)
- Cell Differentiation
- Cells, Cultured
- Diabetes Mellitus
- Glycation End Products, Advanced
(pharmacology)
- Mesenchymal Stem Cells
- Osteogenesis
- Periodontitis
(genetics)
- RNA
(metabolism)
- Adaptor Proteins, Signal Transducing
(genetics)
|