Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Epigallocatechin gallate activates miR-193a-3p and protects mice against glucocorticoid-induced osteoporosis by targeting NFATC1 expression

Ben Dou, Xiaohui Wu, Yisong Xie, Hongliang Ruan, Xiaolan Liu

Department of Orthopedics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China;

For correspondence:- Xiaolan Liu Email: onorouj@yahoo.com Tel:+8613627489118

Accepted: 24 January 2020 Published: 29 February 2020

Citation: Dou B, Wu X, Xie Y, Ruan H, Liu X. Epigallocatechin gallate activates miR-193a-3p and protects mice against glucocorticoid-induced osteoporosis by targeting NFATC1 expression. Trop J Pharm Res 2020; 19(2):227-232 doi: 10.4314/tjpr.v19i2.2

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of epigallocatechin gallate (EGCG) on microRNAs in a mouse model of glucocorticoid-induced osteoporosis (GIOP), and the mechanism involved.

Methods: Osteoclast-specific marker mRNA expressions, receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor κ B (RANK), and miRNA expressions were determined using reverse transcription polymerase chain reaction (RT-qPCR) analysis. Western blotting was used to assay protein expressions, while miRNA and 3’UTR interaction studies were carried out with reporter assay.

Results: Treatment with EGCG resulted in downregulation of glucocorticoid-induced expressions of RANKL, RANK and osteoclast-specific markers i.e. tumor necrosis factor receptor-associated factor 6, (TRAF6), nuclear factor of activated T cells 1 (NFATc1), cathepsin K, matrix metallopeptidase 9 (MMP9) and tartrate-resistant acid phosphatase (TRAP). Furthermore, EGCG treatment significantly reduced reactive oxygen species (ROS) levels and inflammatory cytokine expressions in GIOP mice. The expression of miRNA-targeting osteoclast marker mmu-mir-193-3p was significantly down-regulated in GIOP mice. However, EGCG treatment increased mmu-mir-193-3p expression and had specific interaction with NFATc1 3’UTR (3’-untranslated region). In vitro results showed that mmu-mir-193-3p mimics downregulated dexamethasone (DXM)-induced osteoclast-specific marker expressions.

Conclusion: These results show that EGCG exerts a protective role against GIOP by upregulating miR-193a-3p expressions.

Keywords: Epigallocatechin gallate, Glucocorticoids, RANKL, Osteoporosis