从牙上皮到牙乳头的AKT促进成牙本质细胞分化。

AKT from dental epithelium to papilla promotes odontoblast differentiation.

作者信息

Wang Jiangyi, Lin Xiaoyu, Shen Zongshan, Li Guoqing, Hu Lei, Li Qiong, Li Yang, Wang Jinsong, Zhang Chunmei, Wang Songlin, Wu Xiaoshan

机构信息

Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China.

Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, China; Department of Prosthodontics, Capital Medical University School of Stomatology, Beijing, 100050, China.

出版信息

Differentiation. 2023 Nov-Dec;134:52-60. doi: 10.1016/j.diff.2023.10.002. Epub 2023 Oct 21.

DOI:10.1016/j.diff.2023.10.002

PMID:37898102

Abstract

Epithelial-mesenchymal interactions occur during tooth development. The dental epithelium (DE) is regarded as the signal center that regulates tooth morphology. However, the mechanism by which DE regulates the differentiation of mesenchyme-derived dental papilla (DP) into odontoblasts remains unclear. Using miniature pigs as a model, we analyzed the expression profiles of the DE and DP during odontoblast differentiation using high-throughput RNA sequencing. The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is one of the most enriched pathways in both DE and DP. The PI3K/AKT pathway was first activated in the inner enamel epithelium but not in the DP on embryonic day 50. This pathway was then activated in the odontoblast layer on embryonic day 60. We showed that AKT activation promoted odontoblast differentiation of DP cells. We further demonstrated that activation of PI3K/AKT signaling in the DE effectively increased the expression levels of AKT and dentin sialophosphoprotein in DP cells. Additionally, we found that DE cells secreted collagen type IV alpha 6 chain (COL4A6) downstream of epithelial AKT signaling to positively regulate mesenchymal AKT levels. Therefore, our data suggest that PI3K/AKT signaling from the DE to the DP promotes odontoblast differentiation via COL4A6 secretion.

摘要

上皮-间充质相互作用发生在牙齿发育过程中。牙上皮（DE）被视为调节牙齿形态的信号中心。然而，DE调节间充质来源的牙乳头（DP）向成牙本质细胞分化的机制仍不清楚。我们以小型猪为模型，使用高通量RNA测序分析了成牙本质细胞分化过程中DE和DP的表达谱。磷脂酰肌醇-3-激酶（PI3K）/AKT信号通路是DE和DP中富集程度最高的信号通路之一。PI3K/AKT信号通路在胚胎第50天时首先在内釉上皮中被激活，而在DP中未被激活。然后在胚胎第60天时，该信号通路在成牙本质细胞层被激活。我们发现AKT激活促进了DP细胞向成牙本质细胞的分化。我们进一步证明，DE中PI3K/AKT信号的激活有效地增加了DP细胞中AKT和牙本质涎磷蛋白的表达水平。此外，我们发现DE细胞在上皮AKT信号的下游分泌IV型胶原α6链（COL4A6），以正向调节间充质AKT水平。因此，我们的数据表明，从DE到DP的PI3K/AKT信号通过COL4A6分泌促进成牙本质细胞分化。