ABSTRACT
Extracellular matrix (ECM) is an intricate structure providing the microenvironment niche that influences stem cell differentiation. This study aimed to investigate the efficacy of decellularized ECM derived from human dental pulp stem cells (dECM_DPSCs) and gingival-derived mesenchymal stem cells (dECM_GSCs) as an inductive scaffold for osteogenic differentiation of GSCs. The proteomic analysis demonstrated that common and signature matrisome proteins from dECM_DPSCs and dECM_GSCs were related to osteogenesis/osteogenic differentiation. RNA sequencing data from GSCs reseeded on dECM_DPSCs revealed that dECM_DPSCs upregulated genes related to the Hippo and Wnt signaling pathways in GSCs. In the inhibitor experiments, results revealed that dECM_DPSCs superiorly promoted GSCs osteogenic differentiation, mainly mediated through Hippo and Wnt signaling. The present study emphasizes the promising translational application of dECM_DPSCs as a bio-scaffold rich in favorable regenerative microenvironment for tissue engineering.
Subject(s)
Osteogenesis , Wnt Signaling Pathway , Humans , Osteogenesis/genetics , Proteomics , Dental Pulp , Extracellular Matrix/metabolism , Cell Differentiation , Stem Cells/metabolism , Cell Proliferation , Cells, CulturedABSTRACT
INTRODUCTION: MicroRNAs (miRNAs), small noncoding RNAs, control the translation of messenger RNAs into proteins. miRNAs have a crucial role in regulating the diverse biological processes of many physiological and pathological activities. The aim of this systematic review was to explore various functions of miRNAs in the regulation of dental pulp stem cell (DPSC) behavior. METHODS: The articles were searched in PubMed, SCOPUS, and ISI Web of Science database using designated keywords. Full-length manuscripts published in English in peer-reviewed journals relevant to the role of miRNAs in DPSC functions were included and reviewed by 2 independent researchers. RESULTS: The original search of the database generated 299 studies. A total of 102 duplicate studies were removed. After their exclusion, 48 studies were selected for review. miRNAs have shown to modulate the stemness and differentiation of various mesenchymal stem cells. The miRNAs expression profiles in DPSCs were differed compared with other cell types and have been demonstrated to regulate the levels of proteins crucial for promoting or inhibiting DPSC proliferation as well as differentiation. Further, miRNAs also modulate inflammatory processes in dental pulp. CONCLUSION: miRNAs have various functions on the regulation of DPSCs and understanding these roles of miRNAs is crucial for the development of new therapeutics in regenerative dental medicine. With the advancing technologies, the utilization of miRNA technology could revolutionarily change the future of regenerative endodontics.
Subject(s)
Mesenchymal Stem Cells , MicroRNAs , Cell Differentiation/genetics , Cell Proliferation/genetics , Cells, Cultured , Dental Pulp , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Stem CellsABSTRACT
OBJECTIVE: Wnt signaling is crucial in the physiological and pathological processes of dental pulp tissues. The present study described the effects of Wnt signaling in dental pulp homeostasis and regeneration. DESIGN: Publications in Pubmed and Scopus database were searched, and a narrative review was performed. The roles of Wnt signaling in dental pulp tissue were reviewed and discussed. RESULT: In vitro and in vivo evidence have confirmed the involvement of Wnt signaling in tooth development, dental pulp homeostasis, and physiological processes in dental pulp responses. Manipulating Wnt signaling components generates beneficial effects on pulp healing, dentin repair, and epigenetic regulation related to stemness maintenance, implying that Wnt signaling is a potential therapeutic target for future clinical dental applications. Additionally, an overview of the epigenetic control of dental pulp stem cells by Wnt signaling is provided. CONCLUSION: This review provides basic knowledge on Wnt signaling and outlines its functions in dental pulp tissues, focusing on their potential as therapeutic treatments by targeting the Wnt signaling pathway.
Subject(s)
Dental Pulp , Wnt Signaling Pathway , Cell Differentiation , Dentin , Epigenesis, Genetic , Homeostasis , RegenerationABSTRACT
Although dental pulp and apical papilla are originated from neural crest cells, these tissues exhibit distinct characteristics. Notch signaling is one of the known signaling pathways regulating stemness and behaviors of stem cells. The aim of this study was to examine Notch signaling related gene expression profile comparing between coronal pulp tissues and apical pulp complex. Results demonstrated that coronal pulp tissue had higher expression levels of various genes in Notch pathway. However, NOTCH2, MAML2, DTX4, and NEDD4 mRNA levels were significantly lower in coronal pulp tissue than those of apical pulp complex. Furthermore, dental pulp stem cells (DPSCs) and stem cells isolated from apical papilla (SCAPs) were isolated and characterized. These two cell types exhibited similar mesenchymal stem cell surface markers. DPSCs expressed higher mRNA levels of NOTCH3, NOTCH4, DLL1, and HES1. In addition, SCAPs demonstrated higher colony formation and cell proliferation than DPSCs. In summary, cells and tissues from dental pulp and apical papilla exhibited the distinct gene expression profile of Notch related genes. This could be of one the signaling participated in control of DPSCs and SCAPs cells behaviors.