Department of Developmental Dentistry, School of Dentistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
UBC Faculty of Dentistry, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Cells. 2022 Jul 16;11(14):2216. doi: 10.3390/cells11142216.
BMP signaling plays an important role in dentin development. BMPs and antagonists regulate odontoblast differentiation and downstream gene expression via canonical Smad and non-canonical Smad signaling pathways. The interaction of BMPs with their receptors leads to the formation of complexes and the transduction of signals to the canonical Smad signaling pathway (for example, BMP ligands, receptors, and Smads) and the non-canonical Smad signaling pathway (for example, MAPKs, p38, Erk, JNK, and PI3K/Akt) to regulate dental mesenchymal stem cell/progenitor proliferation and differentiation during dentin development and homeostasis. Both the canonical Smad and non-canonical Smad signaling pathways converge at transcription factors, such as Dlx3, Osx, Runx2, and others, to promote the differentiation of dental pulp mesenchymal cells into odontoblasts and downregulated gene expressions, such as those of DSPP and DMP1. Dysregulated BMP signaling causes a number of tooth disorders in humans. Mutation or knockout of BMP signaling-associated genes in mice results in dentin defects which enable a better understanding of the BMP signaling networks underlying odontoblast differentiation and dentin formation. This review summarizes the recent advances in our understanding of BMP signaling in odontoblast differentiation and dentin formation. It includes discussion of the expression of BMPs, their receptors, and the implicated downstream genes during dentinogenesis. In addition, the structures of BMPs, BMP receptors, antagonists, and dysregulation of BMP signaling pathways associated with dentin defects are described.
BMP 信号在牙本质发育中起着重要作用。BMP 及其拮抗剂通过经典 Smad 和非经典 Smad 信号通路调节成牙本质细胞分化和下游基因表达。BMP 与受体的相互作用导致复合物的形成和信号转导至经典 Smad 信号通路(例如,BMP 配体、受体和 Smads)和非经典 Smad 信号通路(例如,MAPKs、p38、Erk、JNK 和 PI3K/Akt),以调节牙间充质干细胞/祖细胞增殖和分化在牙本质发育和稳态过程中。经典 Smad 和非经典 Smad 信号通路都集中在转录因子上,如 Dlx3、Osx、Runx2 等,以促进牙髓间充质细胞向成牙本质细胞分化,并下调基因表达,如 DSPP 和 DMP1。BMP 信号失调会导致人类多种牙齿疾病。BMP 信号相关基因在小鼠中的突变或敲除导致牙本质缺陷,这使我们能够更好地理解成牙本质细胞分化和牙本质形成的 BMP 信号网络。本综述总结了我们对 BMP 信号在成牙本质细胞分化和牙本质形成中的作用的最新认识。它包括讨论牙本质发生过程中 BMPs、其受体和涉及的下游基因的表达。此外,还描述了 BMPs、BMP 受体、拮抗剂的结构以及与牙本质缺陷相关的 BMP 信号通路的失调。
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