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Downregulation of microRNA‐143‐5p is required for the promotion of odontoblasts differentiation of human dental pulp stem cells through the activation of the mitogen‐activated protein kinases 14‐dependent p38 mitogen‐activated protein kinases signaling pathway
Author(s) -
Wang BaoLiang,
Wang Zhi,
Nan Xi,
Zhang QingCai,
Liu Wei
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27282
Subject(s) - dentin sialophosphoprotein , p38 mitogen activated protein kinases , dental pulp stem cells , microbiology and biotechnology , mapk/erk pathway , downregulation and upregulation , mapk14 , mitogen activated protein kinase , chemistry , protein kinase a , kinase , biology , alkaline phosphatase , stem cell , map kinase kinase kinase , biochemistry , gene , enzyme
MicroRNAs (miRNAs) play critical roles in various biological processes including cell differentiation. Some researchers suggested that the p38 mitogen‐activated protein kinases (MAPK) signaling pathway had an effect on regulating the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). This study focuses on the effects of miR‐143‐5p on hDPSCs by regulating the p38 MAPK signaling pathway. The targeting relationship of MAPK14 and miR‐143‐5p targets were verified by TargetScan and dual‐luciferase reporter gene assay. Through overexpression of miR‐143‐5p or silencing of miR‐143‐5p, expressions of miR‐143‐5p, MAPK14, Ras, MAPK kinase (MKK) 3/6, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteocalcin (OCN) were detected by reverse transcription quantitative polymerase chain reaction. Protein expressions of MAPK14, Ras, and MKK3/6 were determined by western blot analysis. ALP and alizarin red S staining were used to detect mineralization. Initially, MAPK14 was found to be negatively regulated by miR‐143‐5p. Meanwhile, the upregulated miR‐143‐5p decreased the p38 MAPK signaling pathway related genes (MAPK14, Ras, and MKK3/6) and odontoblastic differentiation markers (ALP, DSPP, and OCN) expression. On the contrary, the downregulated miR‐143‐5p increased the p38 MAPK signaling pathway related genes (MAPK14, Ras, and MKK3/6) and odontoblastic differentiation markers (ALP, DSPP, and OCN) expression. Furthermore, ALP activity and mineralized nodules increased after downregulation of miR‐143‐5p, and after its upregulation, ALP activity and mineralized nodules decreased. Our data suggest that poor expression of miR‐143‐5p promotes hDPSCs odontoblastic differentiation through the activation of the p38 MAPK signaling pathway by upregulating MAPK14.