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Exp Cell Res. 2019 May 7. pii: S0014-4827(19)30227-7. doi: 10.1016/j.yexcr.2019.04.036. [Epub ahead of print]

Stromal-derived Factor-1α signaling is involved in bone morphogenetic protein-2-induced odontogenic differentiation of stem cells from apical papilla via the Smad and Erk signaling pathways.

Author information

1
State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, China.
2
Department of Anesthesiology, Shaanxi Province People's Hospital, Xi'an, China.
3
Department of Endodontics, School of Stomatology, China Medical University, Shenyang, China.
4
Stomatology Center, Shenzhen Hospital of Southern Medical University, 1333, Xinhu Road, Bao'an, Shenzhen, Guangdong, PR China.
5
State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, China. Electronic address: weiwang3666@hotmail.com.
6
State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, Fourth Military Medical University, Xi'an, China. Electronic address: yuqing@fmmu.edu.cn.

Abstract

Stromal-derived factor-1α (SDF-1α) is a chemokine signaling molecule that binds to the transmembrane receptor CXC chemokine receptor-4 (CXCR4) and carries out important functions in development tissue homeostasis. SDF-1α signaling via CXCR4 regulates the recruitment of stem and precursor cells to support tissue-specific repair or regeneration. In this study, we examined the contribution of SDF-1α signaling to the odontogenic differentiation of stem cells from the apical papilla (SCAP) induced by bone morphogenic protein 2 (BMP-2). CXCR4 expression was detected in cultured SCAP and SDF-1α promoted the migration of SCAP in Transwell assays. Blocking SDF-1α signaling by treatment with siRNA significantly affected BMP-2-induced mineralized nodule formation and alkaline phosphatase (ALP) activity. Moreover, blocking SDF-1α signaling inhibited the BMP-2-induced early expression of runt-related factor-2 (Runx-2) and strongly suppressed the induction of dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP) expression by BMP-2. Furthermore, the interaction between SDF-1α and BMP-2 signaling was mediated via intracellular Smads and Erk activation. In conclusion, our results demonstrated that SDF-1α can significantly promote the migration of SCAP. Moreover, we revealed corequirement of the SDF-1α/CXCR4 signaling pathways in the BMP-2-induced odontogenic differentiation of SCAP, and these findings may be applied in new strategies for dental pulp regeneration.

KEYWORDS:

Bone morphogenic protein 2; CXC chemokine receptor-4; Odontogenic differentiation; Stem cells from the apical papilla; Stromal-derived factor-1α

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