An Overview of the Use of Medicinal Plants in Regenerative Dentistry

Aim: The oral cavity has the particularity to host multiple hard and soft tissues, in this paper, we will discuss the current therapies that lead to cell differentiation by regenerative therapies and the future alternatives proposed by medicinal plants and all the regenerative potential of these different tissues. Material and Methods: A detailed review of the literature through the various search engines: Scopus, PubMed, google scholar, Cochrane, etc., uses the selected keywords to explore the effect of the regenerative potential of several medicinal plants. Results: Through our research, we have proceeded to sort different medicinal plants, according to their repairing and regenerative potential on the different tissues of the oral cavity. Conclusion: Future studies are conceivable to explore the opportunities and potential provided by medicinal plants in the field of regenerative dentistry.

Nucleus-targeted Dmp1 transgene fails to rescue dental defects in Dmp1 null mice

Dentin matrix protein 1（DMP1） is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with avb3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1M1 V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressingNLSDMP1, in which the endoplasmic reticulum（ER） entry signal sequence of DMP1 was replaced by a nuclear localization signal（NLS） sequence, under the control of a 3.6 kb rat type I collagen promoter plus a 1.6 kb intron 1. We then crossbred theNLSDMP1 transgenic mice with Dmp1 null mice to express the NLSDMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated thatNLSDMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis.

Adult stem cell-based apexogenesis

Generally, the dental pulp needs to be removed when it is infected, and root canal therapy(RCT) is usually required in which infected dental pulp is replaced with inorganic materials(paste and gutta percha). This treatment approach ultimately brings about a dead tooth. However, pulp vitality is extremely important to the tooth itself, since it provides nutrition and acts as a biosensor to detect the potential pathogenic stimuli. Despite the reported clinical success rate, RCT-treated teeth are destined to be devitalized, brittle and susceptible to postoperative fracture. Recently, the advances and achievements in the field of stem cell biology and regenerative medicine have inspired novel biological approaches to apexogenesis in young patients suffer-ing from pulpitis or periapical periodontitis. This review mainly focuses on the benchtop and clinical regeneration of root apex mediated by adult stem cells. Moreover, current strategies for infected pulp therapy are also discussed here.

Phosphorylation of ATF2 promotes odontoblastic differentiation via intrinsic HAT activity

Mouse dental papilla cells(mDPCs)are cranial neural crest-derived dental mesenchymal cells that give rise to dentin-secreting odontoblasts after the bell stage during odontogenesis.The odontoblastic differentiation of mDPCs is spatiotemporally regulated by transcription factors(TFs).Our previous work reveals that chromatin accessibility was correlated with the occupation of the basic leucine zipper TF family during odontoblastic differentiation.However,the detailed mechanism by which TFs regulate the initiation of odontoblastic differentiation remains elusive.Here,we report that phosphorylation of ATF2(p-ATF2)is particularly increased during odontoblastic differentiation in vivo and in vitro.ATAC-seq and p-ATF2 CUT&Tag experiments further demonstrate a high correlation between p-ATF2 localization and increased chromatin accessibility of regions near mineralization-related genes.Knockdown of Atf2 inhibits the odontoblastic differentiation of mDPCs,while overexpression of p-ATF2 promotes odontoblastic differentiation.ATAC-seq after overexpression of p-ATF2 reveals that p-ATF2 increases the chromatin accessibility of regions adjacent to genes associated with matrix mineralization.Furthermore,we find that p-ATF2 physically interacts with and promotes H2BK12 acetylation.Taken together,our findings reveal a mechanism that p-ATF2 promotes odontoblastic differentiation at initiation via remodeling chromatin accessibility and emphasize the role of the phosphoswitch model of TFs in cell fate transitions.

iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel

The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics.This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest(CNC)-like cells(CNCLCs);these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells(iPSCs).CNC is the anterior region of the neural crest in vertebrate embryos,which contains the primordium of dental pulp cells or odontoblasts.The produced CNCLCs showed approximately 2.5-12,000-fold upregulations of major CNC marker genes.Furthermore,the CNCLCs exhibited remarkable odontoblastic differentiation ability,especially when treated with a combination of the fibroblast growth factors(FGFs)FGF4 and FGF9.The FGFs induced odontoblast marker genes by 1.7-5.0-fold,as compared to bone morphogenetic protein 4(BMP4)treatment.In a mouse subcutaneous implant model,the CNCLCs briefly fated with FGF4+FGF9 replicated dental pulp tissue characteristics,such as harboring odontoblast-like cells,a dentin-like layer,and vast neovascularization,induced by the angiogenic self-assembling peptide hydrogel(SAPH),SLan.SLan acts as a versatile biocompatible scaffold in the canal space.This study demonstrated a successful collaboration between regenerative medicine and SAPH technology.