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Updated: Jul 12, 2025
A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
RNA N6-methyladenosine demethylase FTO inhibits glucocorticoid-induced osteoblast differentiation and function in
Lingling Feng1, Wei Zhao2, Yunshan Fan3
1Department of Paediatrics, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, China.
Abstract:
Excess glucocorticoids (GCs) have been reported as key factors that impair osteoblast (OB) differentiation and function. However, the role of RNA N6-methyladenosine (m6 A) in this process has not yet been elucidated. In this study, we report that both the mRNA and protein expression of fat mass and obesity-associated gene (FTO), a key m6 A demethylase, were dose-dependently downregulated during OB differentiation by dexamethasone (DEX) in bone marrow mesenchymal stem cells (BMSCs), and FTO was gradually increased during OB differentiation. Meanwhile, FTO knockdown suppressed OB differentiation and mineralization, whereas overexpression of wide-type FTO, but not mutant FTO (mutated m6 A demethylase active site), reversed DEX-induced osteogenesis impairment. Interfering with FTO inhibited proliferation and the expression of Ki67 and Pcna in BMSCs during OB differentiation, whereas forced expression of wide-type FTO improved DEX-induced inhibition of BMSCs proliferation. Moreover, FTO knockdown reduced the mRNA stability of the OB marker genes Alpl and Col1a1, and FTO-modulated OB differentiation via YTHDF1 and YTHDF2. In conclusion, our results suggest that FTO inhibits the GCs-induced OB differentiation and function of BMSCs.
Insights
Fat mass and obesity-associated gene (FTO) plays a crucial role in bone health. This study reveals FTO inhibits glucocorticoid-induced impairment of osteoblast differentiation and function in bone marrow mesenchymal stem cells.
Area of Science:
- Biochemistry
- Molecular Biology
- Stem Cell Biology
Background:
- Glucocorticoids (GCs) are known to impair osteoblast (OB) differentiation and function.
- The role of RNA N6-methyladenosine (m6A) modification in this process remains unclear.
Purpose of the Study:
- To investigate the role of the m6A demethylase FTO in glucocorticoid-induced impairment of osteoblast differentiation.
- To elucidate the underlying mechanisms of FTO in regulating osteogenesis.
Main Methods:
- Dexamethasone (DEX) treatment of bone marrow mesenchymal stem cells (BMSCs).
- Manipulation of FTO expression (knockdown and overexpression).
- Assessment of OB differentiation, mineralization, and proliferation markers (e.g., Alpl, Col1a1, Ki67, Pcna).
Main Results:
- Dexamethasone downregulated FTO expression in BMSCs during osteoblast differentiation.
- FTO knockdown suppressed OB differentiation and mineralization, while FTO overexpression reversed DEX-induced impairment.
- FTO modulated BMSC proliferation and OB marker gene stability via YTHDF1 and YTHDF2.
Conclusions:
- FTO plays a protective role against glucocorticoid-induced osteoblast dysfunction.
- FTO is a key regulator of osteoblast differentiation and function, potentially through m6A modification.
- Targeting FTO may offer therapeutic strategies for conditions involving glucocorticoid-induced bone loss.
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