位于牙本质-牙髓复合体的界面,成牙本质细胞是专门的细胞,负责响应于外界刺激的牙本质合成和伤害性信号检测。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的形成和重建,它在成牙本质细胞中大量表达。然而,PIEZO1在反动性牙本质生成中的具体作用和潜在机制仍然难以捉摸。在这项研究中,我们在健康人第三磨牙的成牙本质细胞的质膜和细胞质中发现了强烈的PIEZO1表达,小鼠下颌磨牙,和人成牙本质细胞(hOBLCs)。在HOBLCs中,PIEZO1正调控DSPP,DMP1和COL1A1表达经由过程Ca2+/PI3K-Akt/SEMA3A旌旗灯号通路。此外,外源SEMA3A补充有效逆转了PIEZO1敲低hOBLC中降低的矿化能力。在体内,在野生型小鼠牙本质损伤模型中,Piezo1表达在第7天达到峰值,并在第21天恢复到基线,Sema3a呈现类似的表达模式。探讨PIEZO1在成牙本质细胞介导的反应性牙本质生成中的具体作用,在成牙本质细胞中产生了条件敲除Piezo1的小鼠,在对照和条件敲除(cKO)小鼠之间没有观察到牙齿表型的显着差异。然而,cKO小鼠在牙本质损伤后表现出减少的反应性牙本质形成和减少的Sema3a和Dsp阳性染色,表明成牙本质细胞受损的牙髓修复。总之,这些发现表明,PIEZO1通过Ca2+/PI3K-Akt/SEMA3A信号通路在体外增强hOBLC的矿化能力,并有助于体内反应性牙本质生成.
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.