# Effect of Depletion of Developmentally Regulated GTP Binding Protein on Osteoblastic Differentiation and Bone Microarchitecture

## TL;DR

This study shows that reducing DRG2 protein boosts bone formation and strengthens bones in mice, suggesting DRG2 inhibition could help treat bone loss.

## Contribution

The study is the first to show that DRG2 depletion enhances osteoblastic differentiation and improves bone microarchitecture in mice.

## Key findings

- DRG2 inhibition increases bone formation markers and osteoblast transcription factors in MC3T3-E1 cells.
- DRG2 knockout mice show higher bone volume and mineral density in vertebrae and femurs compared to wild-type mice.
- BM-MSCs from DRG2 knockout mice exhibit enhanced osteoblastogenesis under physiological and ovariectomized conditions.

## Abstract

Previous studies have demonstrated that overexpression of DRG2 enhances the osteoclastic activity. However, its impact on osteoblastic differentiation remains unexplored. This study investigates the relationship between DRG2 and osteoblastic activity through in vitro and in vivo studies. DRG2 expression was inhibited in mouse MC3T3‐E1 cells, and its effects on the expression of bone formation markers and osteoblast‐related transcription factors were evaluated. The capacity for osteoblastic differentiation was assessed in mouse preosteoblasts following DRG2 gene knockdown using a short hairpin RNA (shRNA) plasmid. Female C57BL/6N strain DRG2 knockout (KO) mice were generated, and bone phenotypes of the vertebrae and femurs were analysed. Additionally, osteoblastic differentiation capacity was evaluated in bone marrow mesenchymal stem cells (BM‐MSCs) isolated from these mice under physiological and ovariectomized conditions. Inhibition of DRG2 in MC3T3‐E1 cells resulted in upregulation of bone formation markers and osteoblast transcription factors. BM‐MSCs from DRG2 KO mice exhibited significantly higher osteoblastogenesis than wild‐type (WT) mice. DRG2 KO mice demonstrated significantly increased percent bone volume and bone mineral density (BMD) in the vertebra and femur compared to WT mice under physiological and ovariectomized conditions. The inhibition of DRG2 promotes osteoblastic differentiation and is associated with increased BMD, suggesting its potential role in enhancing bone formation.