Fig. 2
From: Runx2 and Nell-1 in dental follicle progenitor cells regulate bone remodeling and tooth eruption
Nell-1’s expression take precedence in CNCCs (cranial neural crest cells), being of great importance in craniofacial tissue development. Nell-1 consists of extremely conservative modules including 5 CR (chordin‐like cysteine‐rich) motifs, a NH2‐terminal TSP‐1 (thrombospondin‐1)‐like motif, a coiled-coil (CC) module, a secretory signal peptide, a laminin G (LamG) module, and 6 EGF (epidermal growth factor)‐like domains (E) including Ca2+-binding EGF-like domains (E*). Runx2 consists of glutamine/alanine-rich region (Q/A); runt homology domain (RUNT); nuclear-localization signal (NLS); proline/serine/threonine-rich region (PST) which is 7 exon. Runx2 target and regulate Nell-1 directly through binding to OSE2 (osteoblast-specific binding element 2) sites in promoter of Nell-1. The Wnt/β-catenin and MAPK signaling pathways have leading role in osteogenesis mediated by Nell-1. Nell-1 stimulates JNK, ERK and p38 in MAPK signaling pathway preferentially and thereby boosts the phosphorylation of Runx2, which positively and circularly activates the expression of Nell-1 and Ocn by matching to the OSE2 elements in promoters. Besides, the active β-catenin in Wnt/β-catenin signaling is also upregulated and nuclear translocated by Nell-1