Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version


Publication Source

Stem Cells





Start Page


Last Page





Neural epidermal growth factor-like (NEL)-like protein 1 (NELL-1) has been identified as an osteoinductive differentiation factor that promotes mesenchymal stem cell (MSC) osteogenic differentiation. In addition to full-length NELL-1, there are several NELL-1-related transcripts reported. We used rapid amplification of cDNA ends to recover potential cDNA of NELL-1 isoforms. A NELL-1 isoform with the N-terminal 240 amino acid (aa) residues truncated was identified. While full-length NELL-1 that contains 810 aa residues (NELL-1810) plays an important role in embryologic skeletal development, the N-terminal-truncated NELL-1 isoform (NELL-1570) was expressed postnatally. Similar to NELL-1810, NELL-1570 induced MSC osteogenic differentiation. In addition, NELL-1570 significantly stimulated MSC proliferation in multiple MSC-like populations such as murine C3H10T1/2 MSC cell line, mouse primary MSCs, and perivascular stem cells, which is a type of stem cells proposed as the perivascular origin of MSCs. In contrast, NELL-1810 demonstrated only limited stimulation of MSC proliferation. Similar to NELL-1810, NELL-1570 was found to be secreted from host cells. Both NELL-1570 expression lentiviral vector and column-purified recombinant protein NELL-1570 demonstrated almost identical effects in MSC proliferation and osteogenic differentiation, suggesting that NELL-1570 may function as a pro-osteogenic growth factor. In vivo, NELL-1570 induced significant calvarial defect regeneration accompanied by increased cell proliferation. Thus, NELL-1570 has the potential to be used for cell-based or hormone-based therapy of bone regeneration. Stem Cells 2015;33:904-915 © 2014 AlphaMed Press.


At the time of publication, author Chenshuang Li was affiliated with the School of Dentistry, University of California. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.


MSC proliferation, NELL-1, Osteogenesis, Secretory protein, Short NELL-1 isoform, Animals, Calcium-Binding Proteins, Cell Differentiation, Cell Line, Cell Proliferation, Glycoproteins, HEK293 Cells, Humans, Male, Mesenchymal Stromal Cells, Mice, Mice, Inbred C3H, Nerve Tissue Proteins, Osteogenesis, Protein Isoforms, Rats, Rats, Sprague-Dawley, Murinae, amino acid, complementary DNA, isoprotein, lentivirus vector, neural epidermal growth factor like (nel) like protein 1, recombinant protein, secretory protein, unclassified drug, calcium binding protein, glycoprotein, isoprotein, Nell1 protein, mouse, Nell1 protein, rat, nerve protein, amino acid sequence, animal cell, animal experiment, animal model, animal tissue, Article, bone development, bone regeneration, cell differentiation, cell population, cell proliferation, cell regeneration, cell stimulation, controlled study, fracture healing, gene amplification, gene expression, host cell, human, human cell, in vivo study, male, mesenchymal stem cell, newborn, nonhuman, protein analysis, protein expression, protein function, rat, animal, biosynthesis, C3H mouse, cell differentiation, cell line, cell proliferation, cytology, genetics, HEK293 cell line, mesenchymal stroma cell, metabolism, mouse, physiology, Sprague Dawley rat

Included in

Dentistry Commons



Date Posted: 10 February 2023

This document has been peer reviewed.