Developmental Endothelial Locus-1 Promotes Osteoclast Differentiation and Activation.

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 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 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 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.