Neural EGFL-like protein 1 (NELL1)

Neural EGFL-like protein 1 (NELL1) is a secreted osteogenic growth factor primarily expressed in skeletal tissues, with powerful effects on bone and cartilage formation, stem cell differentiation, and inhibition of inflammation. Its molecular mechanism involves binding to integrin β1, acting as a ligand for receptors such as CNTNAP4 and Robo2, and driving differentiation via key developmental signaling pathways (MAPK, Wnt/β-catenin, Hedgehog, RUNX family, Notch). It has shown therapeutic potential in preclinical animal models for bone regeneration and osteoarthritis, often in synergy with BMP-2, with the advantages of being anti-adipogenic, anti-inflammatory, and promoting vascularization. Modulation of NELL1 holds promise for treating bone loss diseases, though challenges remain regarding biological stability and potential adverse effects with overexpression.

Other names

Nel-related protein 1NEL-like protein 1NELL1Neural epidermal growth factor-like 1Protein kinase C-binding protein NELL1FLJ45906

Stimulates bone formation via activation of several pathways: MAPK signaling, Wnt/β-catenin pathway, Hedgehog signaling, RUNX2 and RUNX3 transcription factors, Integrin β1-mediated cell adhesion, Modulation of Notch pathway (with isoforms). Inhibits adipogenesis and modulates inflammation in tissue repair.