Midkine Promotes Odontoblast-like Differentiation and Tertiary Dentin Formation

2020 ◽  
Vol 99 (9) ◽  
pp. 1082-1091 ◽  
Author(s):  
Y.H. Park ◽  
Y.S. Lee ◽  
Y.M. Seo ◽  
H. Seo ◽  
J.S. Park ◽  
...  

Autophagy is an intracellular self-degradation process that is essential for tissue development, cell differentiation, and survival. Nevertheless, the role of autophagy in tooth development has not been definitively identified. The goal of this study was to investigate how autophagy is involved in midkine (MK)–mediated odontoblast-like differentiation, mineralization, and tertiary dentin formation in a mouse tooth pulp exposure model. In vitro studies show that MK and LC3 have similar expression patterns during odontoblast-like cell differentiation. Odontoblast-like cell differentiation is promoted through MK-mediated autophagy, which leads to increased mineralized nodule formation. Subcutaneous transplantation of hydroxyapatite/tricalcium phosphate with rMK-treated human dental pulp cells led to dentin pulp–like tissue formation through MK-mediated autophagy. Furthermore, MK-mediated autophagy induces differentiation of dental pulp cells into odontoblast-like cells that form DSP-positive tertiary dentin in vivo. Our findings may provide 1) novel insight into the role of MK in regulating odontoblast-like differentiation and dentin formation in particular via autophagy and 2) potential application of MK in vital pulp therapy.

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5808 ◽  
Author(s):  
Yanjing Ou ◽  
Yi Zhou ◽  
Shanshan Liang ◽  
Yining Wang

Background Senescence-related impairment of proliferation and differentiation limits the use of dental pulp cells for tissue regeneration. Deletion of sclerostin improves the dentinogenesis regeneration, while its role in dental pulp senescence is unclear. We investigated the role of sclerostin in subculture-induced senescence of human dental pulp cells (HDPCs) and in the senescence-related decline of proliferation and odontoblastic differentiation. Methods Immunohistochemical staining and qRT-PCR analyses were performed to examine the expression pattern of sclerostin in young (20–30-year-old) and senescent (45–80-year-old) dental pulps. HDPCs were serially subcultured until senescence, and the expression of sclerostin was examined by qRT-PCR analysis. HDPCs with sclerostin overexpression and knockdown were constructed to investigate the role of sclerostin in HDPCs senescence and senescence-related impairment of odontoblastic differentiation potential. Results By immunohistochemistry and qRT-PCR, we found a significantly increased expression level of sclerostin in senescent human dental pulp compared with that of young human dental pulp. Additionally, elevated sclerostin expression was found in subculture-induced senescent HDPCs in vitro. By sclerostin overexpression and knockdown, we found that sclerostin promoted HDPCs senescence-related decline of proliferation and odontoblastic differentiation potential with increased expression of p16, p53 and p21 and downregulation of the Wnt signaling pathway. Discussion The increased expression of sclerostin is responsible for the decline of proliferation and odontoblastic differentiation potential of HDPCs during cellular senescence. Anti-sclerostin treatment may be beneficial for the maintenance of the proliferation and odontoblastic differentiation potentials of HDPCs.


2013 ◽  
Vol 47 (6) ◽  
pp. 534-541 ◽  
Author(s):  
D. S. Kim ◽  
Y. S. Kim ◽  
W. J. Bae ◽  
H. J. Lee ◽  
S. W. Chang ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yoo-Jin Ko ◽  
Kil-Young Kwon ◽  
Kee-Yeon Kum ◽  
Woo-Cheol Lee ◽  
Seung-Ho Baek ◽  
...  

Porphyromonas gingivalisis considered with inducing pulpal inflammation and has lipopolysaccharide (LPS) as an inflammatory stimulator. GV1001 peptide has anticancer and anti-inflammation activity due to inhibiting activation of signaling molecules after penetration into the various types of cells. Therefore, this study examined inhibitory effect of GV1001 on dental pulp cells (hDPCs) stimulated byP. gingivalisLPS. The intracellular distribution of GV1001 was analyzed by confocal microscopy. Real-time RT-PCR was performed to determine the expression levels of TNF-αand IL-6 cytokines. The role of signaling by MAP kinases (ERK and p38) was explored using Western blot analysis. The effect of GV1001 peptide on hDPCs viability was measured by MTT assay. GV1001 was predominantly located in hDPC cytoplasm. The peptide inhibitedP. gingivalisLPS-induced TNF-αand IL-6 production in hDPCs without significant cytotoxicity. Furthermore, GV1001 treatment markedly inhibited the phosphorylation of MAP kinases (ERK and p38) in LPS-stimulated hDPCs. GV1001 may preventP. gingivalisLPS-induced inflammation of apical tissue. Also, these findings provide mechanistic insight into how GV1001 peptide causes anti-inflammatory actions in LPS-stimulated pulpitis without significantly affecting cell viability.


2011 ◽  
Vol 37 (11) ◽  
pp. 1525-1530 ◽  
Author(s):  
Sang-Im Lee ◽  
Kyung-San Min ◽  
Won-Jung Bae ◽  
Young-Man Lee ◽  
So-Youn Lee ◽  
...  

2014 ◽  
Vol 40 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Wei Liu ◽  
Qimei Gong ◽  
Junqi Ling ◽  
Wen Zhang ◽  
Zhaohui Liu ◽  
...  

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