Adrenomedullin Promotes the Proliferation and Inhibits Apoptosis of Dental Pulp Stem Cells Involved in Divergence Pathways

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• 作者：Qiang Zhu ; MD^&lowast ; ; ^&dagger ; ; Gang Tian ; MD^&dagger ; ; Zhen Tang ; MD^&dagger ; ; Jianyong Gao ; MD^&dagger ; ; Yinghui Tan ; MD^&lowast ; ; ^{tanyinghui2015@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Adrenomedullin ; apoptosis ; proliferation ; pulp stem cells
• 刊名：Journal of Endodontics
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：42
• 期：9
• 页码：1347-1354
• 全文大小：2307 K

文摘

Adrenomedullin (ADM) is highly expressed in dental tissues at the critical developmental time points during tooth development. However, its role in pulp repair and pulp injury is still unknown. The study aimed to investigate the mechanisms by which ADM affects the proliferation and apoptosis of human dental pulp stem cells (DPSCs).

Methods

Fifty-four freshly extracted wisdom teeth were obtained from 27 patients with caries and 27 without. Enzyme-linked immunosorbent assay and immunohistochemistry were used to examine the expression levels of ADM in caries and normal pulp tissues. Human primary DPSCs from the third passage were incubated with ADM (10⁻⁸ mol/L) for 24 hours; the cell cycle and apoptosis were investigated by flow cytomery, and protein expression was investigated using Western blot analysis.

Results

The levels of ADM in caries pulp tissues were significantly higher than those in normal pulp tissues. Incubation with ADM enhanced the percentage of G2/S/M phase DPSCs (P < .01) by the addition of a JNK/c-Jun inhibitor. Incubation with ADM reduced DPSC apoptosis by the addition of the Src/glycogen synthase kinase-3 inhibitor. ADM also ameliorated CoCl₂-induced apoptosis and caspase-3 expression.

Conclusions

ADM enhances the proliferation of DPSCs through activation of the JNK/c-Jun signaling pathway and inhibits apoptosis of DPSCs through activation of the Src/glycogen synthase kinase-3 signaling pathway.