# Transcription factor GTF2I regulates osteoclast differentiation through mediating miR‐134‐5p and MAT2A expressions

## TL;DR

This study shows how the GTF2I gene helps control osteoclast development by regulating miR-134-5p and MAT2A, which could impact bone health.

## Contribution

The novel finding is that GTF2I regulates osteoclast differentiation through the miR-134-5p/MAT2A axis, both in vitro and in vivo.

## Key findings

- GTF2I overexpression reduces osteoclast number and size by suppressing differentiation.
- miR-134-5p is regulated by GTF2I and negatively controls MAT2A expression.
- GTF2I overexpression protects against bone loss in ovariectomized mice.

## Abstract

This study explored the possible effect of transcription factor GTF2I on the differentiation of osteoclasts and its regulation on the miR‐134‐5p/MAT2A axis. RANKL‐induced osteoclasts were measured for expressions of GTF2I, miR‐134‐5p, and MAT2A. The number and size of osteoclasts were assessed after TRAP staining. The expressions of osteoclast differentiation biomarkers, NFATC1, TRAP, and CTSK, were detected as well. The relationships of the GTF2I/miR‐134‐5p/MAT2A axis were verified by ChIP, dual luciferase, and RNA pull‐down assay. In vivo experiments were conducted on ovariectomized (OVX)‐treated mice to determine the effect of GTF2I overexpression on osteoclast differentiation and bone loss. RANKL‐induced osteoclasts had suppressed expressions of GTF2I and miR‐134‐5p and increased expression of MAT2A. GTF2I overexpression or miR‐134‐5p overexpression contributed to decreased cell number and size and suppressed cell differentiation, whereas such an effect can be abolished by overexpression of MAT2A. GTF2I can bind the miR‐134‐5p promoter to regulate its expression, whereas miR‐134‐5p can negatively regulate MAT2A expression. The protective effect of GTF2I overexpression against bone loss and cell differentiation was verified by in vivo experiments. Collectively, these results indicate that GTF2I can mediate miR‐134‐5p expression to increase MAT2A expression, contributing to the suppression of osteoclast differentiation.