Over 90% of the U.S. adult population suffers from tooth structure loss due to caries. Most of the mineralized tooth structure is composed of dentin, a material produced and mineralized by ectomesenchyme derived cells known as odontoblasts. Clinicians, scientists, and the general public share the desire to regenerate this missing tooth structure. To bioengineer missing dentin, increased understanding of human tooth development is required. Here we interrogate at the single cell level the signaling interactions that guide human odontoblast and ameloblast development and which determine incisor or molar tooth germ type identity. During human odontoblast development, computational analysis predicts that early FGF and BMP activation followed by later HH signaling is crucial. Application of this sci-RNA-seq analysis generates a differentiation protocol to produce mature hiPSC derived odontoblasts (iOB). Further, we elucidate the critical role of FGF signaling in odontoblast maturation and its biomineralization capacity using the designed FGFR1/2c isoform specific minibinder scaffolded as a C6 oligomer that acts as a pathway agonist. We find that FGFR1c is upregulated in functional odontoblasts and specifically plays a crucial role in driving odontoblast maturity. Using computational tools, we show on a molecular level how human molar development is delayed compared to incisors. We reveal that enamel knot development is guided by FGF and WNT in incisors and BMP and ROBO in the molars, and that incisor and molar ameloblast development is guided by FGF, EGF and BMP signaling, with tooth type specific intensity of signaling interactions. Dental ectomesenchyme derived cells are the primary source of signaling ligands responsible for both enamel knot and ameloblast development.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802932 | PMC |
http://dx.doi.org/10.3389/fdmed.2023.1209503 | DOI Listing |
Front Cell Dev Biol
December 2024
Hospital of Stomatology, Jilin University, Changchun, China.
Hereditary dentine disorders are autosomal dominant diseases that affect the development and structure of dentine, leading to various dental abnormalities and influencing the individual's oral health. It is generally classified as dentinogenesis imperfecta (DGI) and dentine dysplasia (DD). Specifically, DGI is characterized by the abnormal formation of dentine, resulting in teeth that are discolored, translucent, and prone to fracture or wear down easily.
View Article and Find Full Text PDFFront Immunol
December 2024
Institute for Molecular Cardiovascular Research (IMCAR), Uniklinik RWTH Aachen, RWTH Aachen University, Aachen, Germany.
Recent demographic developments resulted in an aged society with a rising disease burden of systemic and non-communicable diseases (NCDs). In cardiovascular disease (CVD), a NCD with high morbidity and mortality, recent preventive strategies include the investigation of comorbidities to reduce its significant economic burden. Periodontal disease, an oral bacterial-induced inflammatory disease of tooth-supporting tissue, is regulated in its prevalence and severity by the individual host response to a dysbiotic oral microbiota.
View Article and Find Full Text PDFHeliyon
December 2024
Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, United Arab Emirates.
Oxygen is a fundamental requirement for cellular metabolism. Hypoxia is a state of oxygen deprivation of the tissues. Cells develop numerous adaptive mechanisms to survive hypoxic insult.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai, 200011, China.
Periodontitis, a chronic inflammatory disease, is the leading cause of tooth loss in adults and is one of the most prevalent and complex oral conditions. Oxidative stress induced by the excessive generation of reactive oxygen species (ROS) leads to periodontitis, which is closely associated with pathological processes, including mitochondrial dysfunction of periodontal cells and local immune dysregulation. However, current treatment modalities that target single pathological processes have limited long-term therapeutic effects.
View Article and Find Full Text PDFClin Adv Periodontics
December 2024
Department of Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Background: Recombinant human fibroblast growth factor-2 (rhFGF-2) has been shown to effectively promote the formation of new periodontal tissues, and its efficacy has been demonstrated in clinical settings. Moreover, the clinical and radiographic outcomes in the treatment of periodontal infrabony defects can be improved by using rhFGF-2 in combination with a bone substitute. Here, we present a case of four-wall bone defect in a tooth treated by combination regenerative therapy using rhFGF-2 and beta-tricalcium phosphate (β-TCP).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!