NELL1

Official Full Name

neural EGFL like 1

Organism

Homo sapiens

Gene ID

4745

Background

This gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

Synonyms

NRP1; IDH3GL

Cat.No.	Product Name	Price
CSC-DC010297	Panoply™ Human NELL1 Knockdown Stable Cell Line	Inquiry
CSC-SC010297	Panoply™ Human NELL1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD10695Z	Human NELL1 adenoviral particles	Inquiry

Cat.No.	Product Name	Price
SHH351332	shRNA set against Human NELL1 (NM_006157.3)	Inquiry
SHH351336	shRNA set against Mouse NELL1 (NM_001037906.2)	Inquiry
SHH351340	shRNA set against Rat NELL1 (NM_031069.1)	Inquiry

Cat.No.	Product Name	Price
CDCL137663	Mouse Nell1 ORF clone (NM_001037906.2)	Inquiry
CDCR379565	Rat Nell1 ORF Clone(NM_031069.1)	Inquiry
CDCS412580	Human NELL1 ORF Clone (BC096101)	Inquiry
CDFG013341	Human NELL1 cDNA Clone(NM_201551.1)	Inquiry
CDFG018192	Mouse Nell1 cDNA Clone(NM_001037906.2)	Inquiry
CDFR012543	Rat Nell1 cDNA Clone(NM_031069.1)	Inquiry
MiUTR1M-07598	NELL1 miRNA 3'UTR clone	Inquiry
MiUTR1R-04166	NELL1 miRNA 3'UTR clone	Inquiry
MiUTR3H-04869	NELL1 miRNA 3'UTR clone	Inquiry
MiUTR3H-04870	NELL1 miRNA 3'UTR clone	Inquiry
CDCB191984	Rabbit NELL1 ORF clone (XM_002708985.2)	Inquiry
CDCL137657	Human NELL1 ORF clone (NM_201551.1)	Inquiry
CDCR292102	Human NELL1 ORF Clone(NM_006157.3)	Inquiry
CDCS412579	Human NELL1 ORF Clone (BC069674)	Inquiry

Detailed Information

The NELL-1 (neural EGF-like protein 1) protein is a novel osteogenic factor. The study found that compared with the classical osteogenic inducing factor bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 7 (BMP7), Nell-1 has the advantages of strong osteogenesis specificity, denser induced bone tissue and smaller inflammatory response. It not only avoids the inflammatory response of systemic application of BMPs, but also synergizes with BMPs to enhance the osteogenesis effect. A series of in vitro and in vivo studies in recent years have shown that NELL-1 is a very effective bone growth factor. Compared with other bone growth factors, NELL-1 has a relatively simple biological effect, and its osteoinductive activity is more specific. In addition, it cannot induce the formation of ectopic bone tissue alone, so NELL-1 can have higher biosafety and precision. As a new growth factor, NELL-1 has broad and good application prospects in the treatment of various bone tissue defects and bone regeneration.

Figure 1. Cellular signaling pathways through which NELL-1 works. (Pakvasa, M., et al. 2017)

NELL-1 Protein Promotes Bone-related Signaling Molecules and Signaling Pathways

Wnt/β-catenin signaling has the effect of promoting osteogenesis and inhibiting adipogenesis. Wnt signaling promotes osteogenesis by regulating the expression of Run-related transcription factor 2 (Runx2) and directly and indirectly activating Osterix by fibroblast growth factor (FGF). In addition, Wnt ligands inhibit peroxisome proliferators-activated receptors (PPAR-γ) and CCAAT/enhancer binding protein (C/EBP), which inhibit the generation of fat. It was found that the use of Wnt/β-catenin antagonists Dickkopf-1 (DKK-1) and XAV939 inhibited the induction of Runx2 by human recombinant Nell-1 (rhNell-1), which resulted in the destruction of Nell-1 osteogenesis. The nuclear localization of β-catenin in BMSCs treated with Nell-1 increased, confirming that Nell-1 activates the Wnt pathway.

Both ERK1/2 and JNK signaling pathways belong to the MAPK signaling pathway family. The ERK1/2 signal transduction pathway regulates cell growth and differentiation. The JNK signaling pathway plays an important role in the response of inflammation and apoptosis. The study found that NELL-1 protein promotes osteogenic activity through MAPK signaling pathways such as ERK1/2 and JNK. Studies have found that the addition of NELL-1 protein to BMSCs activates MAPK pathways such as ERK1/2 and JNK, resulting in phosphorylation of Runx2 and facilitating osteogenic differentiation of BMSCs. When the ERK1/2 and JNK signals are blocked, the NELL-1 protein contributes to a decrease in bone formation but does not completely disappear, suggesting that NELL-1 contributes to bone formation only partially through the JNK pathway.

NELL-1 and Osteoporosis

Osteoporosis (OP) is a systemic bone disease characterized by decreased bone mass, decreased bone mass and bone strength, increased bone fragility, and prone to fragility fractures. The study found that the PEGylated product of NELL-1, NELL-PEG, has a long half-life in vivo and is suitable for systemic applications. Zhang et al. infused NELL-PEG into the tail vein of rats and labeled with fluorescein isothiocyanate (FITC) to detect NELLPEG in blood. It was found that the retention time of NELL-PEG in rats was significantly higher than that of naked NELL-1. In addition, this study also demonstrates that NELL-PEG is more stable in vivo than naked NELL-1. Studies by JinHee Kwak et al. showed that MicroCT and DXA analysis showed that systemic infusion of NELL-PEG every 4 or 7 days significantly increased femoral and lumbar BMD and bone volume percentage. Moreover, immunohistochemistry showed a marked increase in osteocalcin expression, and TRAP staining showed a decrease in the number of osteoclasts in the NELL-PEG group. This indicates that NELL-PEG can be stably stored in the body for a long time, and the original osteogenesis of NELL-1 is well exerted.

References:

Pakvasa, M. , Alverdy, A. , Mostafa, S. , Wang, E. , Fu, L. , & Li, A. , et al. (2017). Neural egf-like protein 1 (nell-1): signaling crosstalk in mesenchymal stem cells and applications in regenerative medicine. Genes & Diseases, 4(3), 127-137.
Kwak JH, Zhang YL. (2015). Pharmacokinetics and osteogenic potential of pegylated nell-1 in vivo after systemic administration. Biomaterials, 57, 73-83.
Zhang, Y. , Velasco, O. , Zhang, X. , Ting, K. , Soo, C. , & Wu, B. M. . (2014). Bioactivity and circulation time of pegylated nell-1 in mice and the potential for osteoporosis therapy. Biomaterials, 35(24), 6614-6621.

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