# Developmental Endothelial Locus-1 Promotes Osteoclast Differentiation and Activation

## TL;DR

This study shows that DEL-1 promotes osteoclast development, challenging its previously known anti-inflammatory role and suggesting a new function in bone metabolism.

## Contribution

The paper reveals a novel pro-osteoclastogenic role of DEL-1, contradicting its established anti-inflammatory function.

## Key findings

- Del-1 mRNA levels increase in cells stimulated by RANKL during osteoclastogenesis.
- Recombinant DEL-1 enhances osteoclast differentiation in a dose-dependent manner.
- DEL-1 silencing reduces osteoclast formation, confirming its functional role.

## Abstract

Developmental endothelial locus-1 (DEL-1) has traditionally been characterized within the scientific community as having anti-inflammatory properties with potential inhibitory effects on osteoclast formation. Our investigation challenges this paradigm by examining Del-1 expression in RAW264.7 cells and bone marrow-derived macrophages (BMMs) during osteoclastogenesis, as well as its functional impact on osteoclast development and activity. Our experimental findings revealed that Del-1 mRNA levels were markedly elevated in cells stimulated by the receptor activator of the nuclear factor κB ligand compared to unstimulated precursors. When cultured with varying concentrations of recombinant DEL-1, osteoclast differentiation increased in a dose-dependent manner. Furthermore, BMMs isolated from ovariectomized mice exhibited significantly higher Del-1 mRNA expression than those from control animals. To confirm DEL-1’s role, we employed RNA interference techniques, demonstrating that DEL-1 silencing in RAW264.7 cells substantially reduced osteoclast formation. These results suggest that DEL-1 plays a previously unrecognized role in promoting osteoclastogenesis and may contribute to bone metabolism imbalances in conditions like osteoporosis, highlighting its complex role in skeletal homeostasis and its potential as a therapeutic target.