Nell-1 promotes the neural-like differentiation of dental pulp cells

• Published in: Biochemical and biophysical research communications 2019-05, Vol.513 (2), p.515-521
• Main Authors: Han, Qi, Wang, Qiang, Wu, Jiameng, Li, Mengyue, Fang, Yixuan, Zhu, Hongfan, Wang, Xiaoying
• Format: Article
• Language: English
• Subjects: Animals; Calcium-Binding Proteins - analysis; Calcium-Binding Proteins - metabolism; Cell Differentiation; Cells, Cultured; Dental Pulp - cytology; Dental Pulp - innervation; Dental Pulp - metabolism; Human dental pulp stem cell; Humans; Nel-like molecule-1; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - metabolism; Neural-like differentiation; Neurogenesis; Rats, Wistar; Stem Cells - cytology; Stem Cells - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.04.028

Previous studies showed that Nel-like molecule-1 (Nell-1) can positively regulate odontoblastic differentiation and dentin formation. Intriguingly, our group found that Nell-1 is co-expressed with neural markers. The purpose of this study was to investigate whether Nell-1 protein plays a regulatory role in the differentiation of dental pulp cells into neural-like cells by in vivo and in vitro studies. The expression patterns of Nell-1 and dental pulp neural markers were observed by double immunofluorescence staining in normal dental pulp tissue sections of Wistar rat. Collagen sponge containing Nell-1 protein was added into the pulp cavity of rat molars in order to observe the expression patterns of neural markers in rat dental pulp repair and regeneration model by immunohistochemical staining. Moreover, human dental pulp stem cells (hDPSCs) were cultured, and different concentrations of Nell-1 protein were added for 12 h, 24 h, and 72h. The expression of neural markers was detected by using quantitative real-time polymerase chain reaction and Western blot. Nell-1 was co-expressed with neural markers including substance P (SP) and Nestin in rat dental pulp tissue. The expression of neural markers including SP, neuron-specific enolase (NSE), and Nestin was increased obviously in rat dental pulp tissues stimulated with Nell-1 protein. In cultured hDPSCs induced by Nell-1 protein, the expression of neural markers including glial fibrillary acidic protein (GFAP), Nestin, and β-III tubulin was increased. Nell-1 plays a positive role in inducing the differentiation of DPSCs into neural-like cells. •Nell-1 is co-expressed with neural markers in pulp, which indicates that Nell-1 might be expressed in dental pulp nerve.•The expression levels of neural markers were increased in rat pulp and in cultured hDPSCs stimulated with Nell-1 protein.•This is the first study to demonstrate the effect of Nell-1 on dental pulp cells neural-like differentiation.