PIEZO1 Promotes Odontoblast-Mediated Reactionary Dentinogenesis via SEMA3A.

Journal of dental research Pub Date : 2024-08-01 Epub Date: 2024-06-24 DOI:10.1177/00220345241257866
P Huang, R X Jiang, F Wang, W W Qiao, Y T Ji, L Y Meng, Z Bian
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Abstract

Located at the interface of the dentin-pulp complex, the odontoblasts are specialized cells responsible for dentin synthesis and nociceptive signal detection in response to external stimuli. Recent studies have shown that the mechanosensitive ion channel PIEZO1 is involved in bone formation and remodeling through the influx of calcium ions, and it is abundantly expressed in odontoblasts. However, the specific role of PIEZO1 in reactionary dentinogenesis and the underlying mechanisms remain elusive. In this study, we found intense PIEZO1 expression in the plasma membrane and cytoplasm of odontoblasts in healthy human third molars, mouse mandibular molars, and human odontoblast-like cells (hOBLCs). In hOBLCs, PIEZO1 positively regulated DSPP, DMP1, and COL1A1 expression through the Ca2+/PI3K-Akt/SEMA3A signaling pathway. In addition, exogenous SEMA3A supplementation effectively reversed reduced mineralization capacity in PIEZO1-knockdown hOBLCs. In vivo, Piezo1 expression peaked at day 7 and returned to baseline at day 21 in a wild-type mice dentin injury model, with Sema3a presenting a similar expression pattern. To investigate the specific role of PIEZO1 in odontoblast-mediated reactionary dentinogenesis, mice with a conditional knockout of Piezo1 in odontoblasts were generated, and no significant differences in teeth phenotypes were observed between the control and conditional knockout (cKO) mice. Nevertheless, cKO mice exhibited reduced reactionary dentin formation and decreased Sema3a and Dsp positive staining after dentin injury, indicating impaired dental pulp repair by odontoblasts. In summary, these findings suggest that PIEZO1 enhances the mineralization capacity of hOBLCs in vitro via the Ca2+/PI3K-Akt/SEMA3A signaling pathway and contributes to reactionary dentinogenesis in vivo.

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PIEZO1 通过 SEMA3A 促进牙本质母细胞介导的反应性牙本质生成
牙本质母细胞位于牙本质-牙髓复合体的界面,是负责牙本质合成和对外界刺激的痛觉信号检测的特化细胞。最近的研究表明,机械敏感性离子通道 PIEZO1 通过钙离子的流入参与骨形成和重塑,它在牙本质母细胞中大量表达。然而,PIEZO1 在反应性牙本质形成中的具体作用及其内在机制仍未确定。在这项研究中,我们发现 PIEZO1 在健康人类第三磨牙、小鼠下颌磨牙和人类牙本质母细胞样细胞(hOBLCs)的牙本质母细胞的质膜和细胞质中都有大量表达。在hOBLCs中,PIEZO1通过Ca2+/PI3K-Akt/SEMA3A信号通路正向调节DSPP、DMP1和COL1A1的表达。此外,补充外源 SEMA3A 能有效逆转 PIEZO1 敲除的 hOBLCs 矿化能力的降低。在体内,野生型小鼠牙本质损伤模型中,Piezo1的表达在第7天达到峰值,在第21天恢复到基线水平,Sema3a也呈现类似的表达模式。为了研究 PIEZO1 在牙本质母细胞介导的反应性牙本质生成中的特殊作用,我们在牙本质母细胞中产生了条件性敲除 Piezo1 的小鼠,在对照组和条件性敲除(cKO)小鼠之间没有观察到牙齿表型的显著差异。然而,cKO 小鼠的反应性牙本质形成减少,牙本质损伤后 Sema3a 和 Dsp 阳性染色减少,表明牙本质母细胞的牙髓修复功能受损。总之,这些研究结果表明,PIEZO1在体外通过Ca2+/PI3K-Akt/SEMA3A信号通路增强了hOBLCs的矿化能力,并有助于体内的反应性牙本质形成。
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