The effect of TNFα on human dental pulp stem cells
Date Issued
2011
Date
2011
Author(s)
Hsu, Yu-Chiao
Abstract
Dental caries is the most prevalent infectious disease in the world. The byproduct of dentin matrix demineralization by bacterial acid, and the bacterial endotoxin, lipopolysaccharide(LPS) would stimulate the immune system cells within the pulp to release proinflammatory cytokines and recruit of more lymphocytes. Moreover, a series of inflammatory response would occur. The proinflammatory cytokines found within the pulp comprise the increased level of interlukin((interlukin-1α、interlukin-1βand interlukin-8) and TNFα. In the past research we found that MAP4K4 (Mitogen-activated protein kinase kinase kinase kinase 4) is up-regulated during the mineralized differentiation process of dental pulp stem cell. Recent study also revealed that MAPK regulate not only the mineralization process, but also apoptosis and necrosis. It was also found that TNFα can activate MAP4K4 signaling pathway .We therefore hypothesized that TNFα may affect the mineralization process through activation of MAP4K4.
The purpose of the study is to investigate the effect of TNFα on human dental pulp stem cells. The materials and methods used in this study was treating dental pulp stem cell with TNFα for different time periods to see the effects on the expression of ALP by staining and the activation of ALP was also measured. Then, we treat dental pulp stem cell with TNFα and see the effect on the cytoplasm level of MAP4K4 and p-MAP4K4 thr`ough indirect ELISA. At last, MAPK inhibitor is added in to make sure the expression of ALP activity.
Our result indicated that by treating with TNFα for a long period, the mineralization of dental pulp stem stem cells were inhibited, but the mineralization expression is enhanced after short time treatment with TNFα. With ELISA analysis, TNFα promotes the activation of MAP4K4 was shown. When MAPK siRNA is inserted, the expression of ALP activity is downregulated, with or without adding TNFα to the culture medium . It is concluded that TNFα will promote the mineralized differentiation via MAP4K4 signaling pathway in short time period, but long treated time inhibit cell mineralization and may eventually lead to cell necrosis and apoptosis.
Subjects
Dental pulp stem cell(DPSC)
TNFα
ALP
siRNA
SDGs
Type
thesis
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