BMP Signaling Pathway in Dentin Development and Diseases

Abstract

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.

Antimicrobial and Osteogenic Effects of Collagen Membrane Decorated with Chitosan–Nano-Hydroxyapatite

“…BMP-4 mRNA levels were also increased by CHI–HAp–collagen. BMP-4 is a member of the transforming growth factor superfamily that is important in tooth generation and formation, osteoblast differentiation, and matrix secretion [ 51 ]. On the other hand, the level of RUNX2 mRNA was similar in DPSCs seeded on both membranes.…”

Single-cell transcriptome profiling reveals distinct expression patterns among genes in the mouse incisor dental pulp

“…An interaction between TWIST1 and RUNX2 coordinates craniofacial muscle development (Han et al, 2021). Studies have shown that both the canonical and non-canonical SMAD-dependent signaling pathways control the proliferation and differentiation of dental MSCs as well as osteogenesis and skeletal development (Liu et al, 2022;Wu et al, 2016). Histone deacetylation via HDACs is an important function of the multiprotein epigenetic complexes that interact with many TFs, including RUNX2 and LEF1, during skeletal development (Jensen et al, 2010;Huynh et al, 2017).…”

“…Coordinated crosstalk among the bone morphogenic protein (BMP), fibroblast growth factor (FGF) and WNT signaling pathways from the dental epithelium to the mesenchyme underlies the regulation of the odontogenic regulatory network during early tooth development (Chen et al, 2009). BMP signaling utilizes the canonical and non-canonical SMAD signaling pathways, which engage different TFs including RUNX2 and SP7 to initiate the differentiation of MSCs along the odontoblastic lineage (Liu et al, 2022).…”

Dentin regeneration based on tooth tissue engineering: A review

“…65,68,69 BMP-2 regulates the development of dental pulp stem cells (DSPC) into odontoblast-like cells and promotes the expression of tooth-associated genes. 70 In three dimensional pellet cultures, human recombinant BMP2 prompted the differentiation of pulp stem/ progenitor cells into odontoblasts. 39 Side population (SP) cells from dental pulp cells BMP-2 integrated were autologously transplanted on the amputated pulp and stimulated the production of reparative dentin.…”