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Stem Cell Res Ther. 2019 May 20;10(1):139. doi: 10.1186/s13287-019-1252-7.

Effect of canonical NF-κB signaling pathway on the differentiation of rat dental epithelial stem cells.

Liang Y1,2,3,4, Chen G1,2, Yang Y1,2,5, Li Z1,2, Chen T1,2, Sun W1,2, Yu M1,2, Pan K1,2,3, Guo W6,7,8, Tian W9,10,11.

Author information

1
National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
2
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
3
Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section, Renmin South Road, Chengdu, 610041, People's Republic of China.
4
Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
5
Department of Pediatric Dentistry, West China College of Stomatology, Sichuan University, No.14, 3rd Section, Renmin South Road, Chengdu, 610041, People's Republic of China.
6
National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China. guoweihua943019@163.com.
7
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China. guoweihua943019@163.com.
8
Department of Pediatric Dentistry, West China College of Stomatology, Sichuan University, No.14, 3rd Section, Renmin South Road, Chengdu, 610041, People's Republic of China. guoweihua943019@163.com.
9
National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China. drtwd@sina.com.
10
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China. drtwd@sina.com.
11
Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, No.14, 3rd Section, Renmin South Road, Chengdu, 610041, People's Republic of China. drtwd@sina.com.

Abstract

BACKGROUND:

Nuclear factor-κB (NF-κB), an important transcription factor, participates in many physiological and pathological processes such as growth, differentiation, organogenesis, apoptosis, inflammation, and immune response, including tooth development. However, it is still unknown whether NF-κB participates in the regulation of dental epithelial stem cells (DESCs) in postnatal rat incisors. Here, we investigated the specific differentiation regulatory mechanisms of the canonical NF-κB signaling pathway in DESCs and provided the mechanism of cross-talk involved in DESC differentiation.

METHODS:

After adding the activator or inhibitor of the NF-κB signaling pathway, Western blot and quantitative real-time PCR were used to analyze the expressions of amelogenesis-related genes and proteins and canonical transforming growth factor-β (TGF-β) signaling. In addition, we used amelogenesis induction in vitro by adding the activator or inhibitor of the NF-κB signaling pathway to the amelogenesis-induction medium, respectively. Recombinant TGF-β was used to activate the TGF-β pathway, and SMAD7 siRNA was used to downregulate the expression of SMAD7 in DESCs.

RESULTS:

We found that the expression of amelogenesis-related genes and proteins as well as TGF-β signaling were downregulated, while SMAD7 expression was increased in NF-κB-activated DESCs. In addition, NF-κB-inhibited DESCs exhibited opposite results compared with NF-κB-activated DESCs. Furthermore, the canonical NF-κB signaling pathway suppressed the canonical TGF-β-SMAD signaling by inducing SMAD7 expression involved in the regulation of DESC differentiation.

CONCLUSIONS:

These results indicate that the canonical NF-κB signaling pathway participated in the regulation of DESC differentiation, which was through upregulating SMAD7 expression and further suppressing the canonical TGF-β-SMAD signaling pathway.

KEYWORDS:

Amelogenesis; Dental epithelial stem cell; Differentiation; NF-κB; TGF-β

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