Departmental Papers (Dental)
Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells Induced by a Short Isoform of NELL-1
Date of this Version
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.
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Pang, S., Shen, J., Chen, F., Zheng, Z., James, A. W., Hsu, C., Zhang, H., Lee, K. S., Wang, C., Lee, C., Chen, X., Jia, H., Zhang, X., Soo, C., & Ting, K. (2015). Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells Induced by a Short Isoform of NELL-1. Stem Cells, 33 (3), 904-915. http://dx.doi.org/10.1002/stem.1884
Date Posted: 10 February 2023
This document has been peer reviewed.
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.