Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells Induced by a Short Isoform of NELL-1
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Subject
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
Dentistry
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Abstract
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.