DNMT3a Promotes Osteoblast Differentiation and Alleviates Osteoporosis Via the PPARγ/SCD1/GLUT1 axis

Abstract

Background: This study was designed to elucidate the role of DNMT3a and PPARγ functions in postmenopausal osteoporosis. Materials&methods: Mice were ovariectomized to establish an in vivo osteoporosis model and MC3T3-E1-14 osteoblasts were induced to differentiate. Gain- or loss-of-function approaches were used to manipulate the expression of PPARγ, DNMT3a and SCD1, followed by an evaluation of their role in postmenopausal osteoporosis both in vivo and in vitro. Results:DNMT3a induced methylation of the PPARγ promoter region, consequently stimulating osteoblast differentiation. PPARγ elevated SCD1, which decreased GLUT1 and inhibited osteoblast differentiation. Inhibition of PPARγ reduced SCD1 while increasing GLUT1 expression, thus alleviating postmenopausal osteoporosis in mice. Conclusion:DNMT3a promotes osteoblast differentiation and prevents postmenopausal osteoporosis by regulating the PPARγ/SCD1/GLUT1 axis.

Keywords::

• DNA methyltransferase 3A
• glucose transporter 1
• methylation
• osteoblast differentiation
• peroxisome proliferator-activated receptor γ
• postmenopausal osteoporosis
• PPARγ
• stearoyl-coenzyme A desaturase 1

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0391

Author contributions

LJ Lu and LJ Wang designed the study. JQ Wu and MJ Yang collated the data. BH Chen and HH Wang contributed to drafting the manuscript. KF Gan collected and provided the sample for this study and revised the figures. All authors read and approved the final submitted manuscript.

Acknowledgments

The authors thank American Journal Experts for English language editing.

Financial&competing interests disclosure

This work was supported by the Medical Science and Technology Project of Ningbo (no. 2019Y04), and the Natural Science Foundation of Ningbo (no. 2014A610252). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Paid editing/writing assistance was provided by American Journal Experts.

Ethical conduct of research

The study protocol was approved by the Ethics Committee of the authors’ hospital. All participants provided signed informed consent. The animal experiments were conducted under the approval of the Animal Ethics Committee of the authors’ hospital and in strict accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health. Due efforts were made to reduce animal pain.

Data availability statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Additional information

Funding

This work was supported by the Medical Science and Technology Project of Ningbo (no. 2019Y04), and the Natural Science Foundation of Ningbo (no. 2014A610252). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in themanuscript apart from those disclosed.