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Journal of Dental Sciences Apr 2024Dental pulp stem cells (DPSCs) exhibit versatile differentiation capabilities, including neural differentiation, prompting the hypothesis that they may be implicated in...
BACKGROUND/PURPOSE
Dental pulp stem cells (DPSCs) exhibit versatile differentiation capabilities, including neural differentiation, prompting the hypothesis that they may be implicated in the neurodevelopment of teeth. This study aimed to explore the temporospatial dynamics between DPSCs and tooth innervation, employing immunofluorescence staining and fluorescent dye injections to investigate the distribution of DPSCs, neural stem cells (NSCs), nerve growth cones, and sensory nerves in developing mouse tooth germs at various stages.
MATERIALS AND METHODS
Immunofluorescence staining targeting CD146, Nestin, and GAP-43, along with the injection of AM1-43 fluorescent dye, were utilized to observe the distribution of DPSCs, NSCs, nerve growth cones, and sensory nerves in mouse tooth germs at different developmental stages.
RESULTS
Positive CD146 immunostaining was observed in microvascular endothelial cells and pericytes within and around the tooth germ. The percentage of CD146-positive cells remained consistent between 4-day-old and 8-day-old second molar tooth germs. Conversely, Nestin expression in odontoblasts and their processes decreased in 8-day-old tooth germs compared to 4-day-old ones. Positive immunostaining for GAP-43 and AM1-43 fluorescence revealed the entry of nerve growth cones and sensory nerves into the pulp in 8-day-old tooth germs, while these elements were confined to the dental follicle in 4-day-old germs. No co-localization of CD146-positive DPSCs with nerve growth cones and sensory nerves was observed.
CONCLUSION
DPSCs and NSCs were present in dental pulp tissue before nerves penetrated the pulp. The decline in NSCs after nerve entry suggests a potential role for DPSCs and NSCs in attracting neural growth and/or differentiation within the pulp.
PubMed: 38618089
DOI: 10.1016/j.jds.2024.02.007 -
Materials Today. Bio Dec 2023Conventional dentistry faces limitations in preserving tooth health due to the finite lifespan of restorative materials. Regenerative dentistry, utilizing stem cells and... (Review)
Review
Conventional dentistry faces limitations in preserving tooth health due to the finite lifespan of restorative materials. Regenerative dentistry, utilizing stem cells and bioactive materials, offers a promising approach for regenerating dental tissues. Human dental pulp stem cells (hDPSCs) and bioactive materials like calcium phosphate (CaP) and silicate-based materials have shown potential for dental tissue regeneration. This systematic review aims to investigate the effects of CaP and silicate-based materials on hDPSCs through in vitro studies published since 2015. Following the PRISMA guidelines, a comprehensive search strategy was implemented in PubMed MedLine, Cochrane, and ScienceDirect databases. Eligibility criteria were established using the PICOS scheme. Data extraction and risk of bias (RoB) assessment were conducted, with the included studies assessed for bias using the Office of Health and Translation (OHAT) RoB tool. The research has been registered at OSF Registries. Ten in vitro studies met the eligibility criteria out of 1088 initial studies. Methodological heterogeneity and the use of self-synthesized biomaterials with limited generalizability were observed in the included study. The findings highlight the positive effect of CaP and silicate-based materials on hDPSCs viability, adhesion, migration, proliferation, and differentiation. While the overall RoB assessment indicated satisfactory credibility of the reviewed studies, the limited number of studies and methodological heterogeneity pose challenges for quantitative research. In conclusion, this systematic review provides valuable insights into the effects of CaP and silicate-based materials on hDPSCs. Further research is awaited to enhance our understanding and optimize regenerative dental treatments using bioactive materials and hDPSCs, which promise to improve patient outcomes.
PubMed: 37779917
DOI: 10.1016/j.mtbio.2023.100815 -
Anatomia, Histologia, Embryologia Sep 2023Mesenchymal stem cells (MSCs) are used for regenerative therapy. Dental pulp MSCs make extracted wisdom teeth a useful resource in humans. Preclinical validation of...
Mesenchymal stem cells (MSCs) are used for regenerative therapy. Dental pulp MSCs make extracted wisdom teeth a useful resource in humans. Preclinical validation of regenerative therapies requires large animal models such as the sheep. Since stem cells can be retrieved from the dental pulp of ovine incisors, the best age to extract a maximal volume of dental pulp needs to be defined. The objective of this ex vivo study was to quantify incisors dental pulp volume, in sheep of various age. Three jaws were dedicated to histology (one per age group); the others were imaged with a computed tomography scanner [3 years-old (n = 9), 4 (n = 3) and 6 (n = 5)]. The incisors dental pulp volume was measured after 3D reconstruction. Multiple linear regression showed that dental pulp volume of ovine incisors decreases with age (β-estimate = -3.3; p < 0.0001) and teeth position from the more central to the more lateral (β-estimate = -4.9; p = 0.0009). Weight was not a relevant variable in the regression model. The dental pulp volume ranged from 36.7 to 19.6 mm in 3-year-old sheep, from 23.6 to 11.3 in 4-year-old sheep, and from 19.4 to 11.5 in 6-year-old sheep. The pulp volume of the most central teeth (first intermediate) was significantly higher than the most lateral teeth (corner). Haematoxylin-Eosin-Safran of the whole incisors, and of isolated dental pulps demonstrated a similar morphology to that in humans. The first intermediate incisor of 3-year-old sheep should be selected preferentially in preclinical research to retrieve the highest volume of dental pulp.
Topics: Sheep; Humans; Animals; Incisor; Dental Pulp; Linear Models; Mesenchymal Stem Cells
PubMed: 37278128
DOI: 10.1111/ahe.12935 -
Clinical Oral Investigations Oct 2023The purpose of this study was to investigate the oxidative stress cycle consisting of reactive oxygen molecules (ROS), glutathione (GSH) and glutathione S-transferase...
OBJECTIVES
The purpose of this study was to investigate the oxidative stress cycle consisting of reactive oxygen molecules (ROS), glutathione (GSH) and glutathione S-transferase (GST) in caries-related pulp inflammation.
METHODOLOGY
Fifty-four pulp tissue samples were collected from healthy donors with the diagnosis of reversible pulpitis, symptomatic irreversible pulpitis, and healthy pulp. Twelve pulp samples from each group were homogenized and total protein, ROS, GSH, and GST were measured by spectrophotometer. The remaining 6 samples from each group were prepared for paraffin block and used for the histopathologic and immunohistochemical evaluation of oxidative stress parameters and TUNEL labeling. Data were analyzed statistically.
RESULTS
The results revealed that total protein levels significantly decreased; however, ROS levels increased in both reversible and irreversible pulpitis compared to the healthy pulp (p < 0.01). Also, as inflammation increases, GST enzyme levels decrease while GSH levels increase significantly (p < 0.05). It was found that the number of TUNEL (+) cells was increased in irreversible pulpitis samples compared to healthy and reversible pulpitis groups (p < 0.05). GSTP1 and GSH immunoreactivity were also observed in irreversible pulpitis samples.
CONCLUSIONS
It has been revealed that caries-related inflammation alters the oxidative stress cycle in dental pulp tissue. The increase in GSH levels in the inflamed dental pulp due to the increase in ROS levels may improve the defensive ability of the dental pulp.
CLINICAL RELEVANCE
There is a relationship between oxidative stress and inflammation. Control of excessive oxidative stress in pulpitis can stimulate reparative and regenerative processes. The present findings may provide an overview of the management of oxidative stress in cases with pulpitis during regenerative treatments.
Topics: Humans; Pulpitis; Dental Pulp; Reactive Oxygen Species; Inflammation; Dental Caries; Oxidative Stress
PubMed: 37642737
DOI: 10.1007/s00784-023-05203-y -
International Journal of Medical... 2024Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to...
Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to explore whether hypoxic dental pulp stem cells (DPSCs) can promote osteoclastogenesis in orthodontically induced inflammatory root resorption (OIIRR). Succinate in the supernatant of DPSCs under normal and hypoxic conditions was measured by a succinic acid assay kit. The culture supernatant of hypoxia-treated DPSCs was used as conditioned medium (Hypo-CM). Bone marrow-derived macrophages (BMDMs) from succinate receptor 1 (SUCNR1)-knockout or wild-type mice were cultured with conditioned medium (CM), exogenous succinate or a specific inhibitor of SUCNR1 (4c). Tartrate-resistant acid phosphatase (TRAP) staining, Transwell assays, qPCR, Western blotting, and resorption assays were used to evaluate osteoclastogenesis-related changes. The concentration of succinate reached a maximal concentration at 6 h in the supernatant of hypoxia-treated DPSCs. Hypo-CM-treated macrophages were polarized to M1 proinflammatory macrophages. Hypo-CM treatment significantly increased the formation and differentiation of osteoclasts and increased the expression of osteoclastogenesis-related genes, and this effect was inhibited by the specific succinate inhibitor 4c. Succinate promoted chemotaxis and polarization of M1-type macrophages with increased expression of osteoclast generation-related genes. SUCNR1 knockout decreased macrophage migration, M1 macrophage polarization, differentiation and maturation of osteoclasts, as shown by TRAP and NFATc1 expression and cementum resorption. Hypoxic DPSC-derived succinate may promote osteoclast differentiation and root resorption. The regulation of the succinate-SUCNR1 axis may contribute to the reduction in the OIIRR.
Topics: Animals; Mice; Dental Pulp; Osteoclasts; Root Resorption; Humans; Succinic Acid; Osteogenesis; Mice, Knockout; Stem Cells; Cell Differentiation; Macrophages; Cell Hypoxia; Receptors, G-Protein-Coupled; Culture Media, Conditioned; Cells, Cultured
PubMed: 38774749
DOI: 10.7150/ijms.94972 -
Primary Dental Journal Dec 2023Acute dental trauma is unscheduled and presents infrequently to the majority of practitioners. Therefore, a consistent, logical and systematic process for examination,...
Acute dental trauma is unscheduled and presents infrequently to the majority of practitioners. Therefore, a consistent, logical and systematic process for examination, prioritisation and management is imperative for all sustained injuries to have an optimal outcome. Fractures are a frequent sequela to dental trauma and can involve any aspect of the tooth structure or supporting alveolar bone. While some minor crown fractures may initially seem inconsequential, they may be a subtle indication to a more serious underlying root fracture. Concomitant injuries and injuries that have been initially missed are generally associated with poorer outcomes. The time sensitive management of traumatic dental injuries aims to preserve pulpal and periodontal health where possible. The follow up period for tooth or alveolar fractures are important to allow for early intervention if pathology develops.
Topics: Humans; Tooth Avulsion; Tooth Root; Tooth Crown; Tooth Fractures; Dental Pulp
PubMed: 38018681
DOI: 10.1177/20501684231212376 -
Cell Proliferation Jan 2024Dental pulp injury remains a clinical challenge with limited therapeutic approaches. In the present study, we sought to prove that dental pulp stromal cells (DPSCs)...
Dental pulp injury remains a clinical challenge with limited therapeutic approaches. In the present study, we sought to prove that dental pulp stromal cells (DPSCs) mitochondrial transfer could promote dental pulp injury repair and endoplasmic reticulum (ER)-mitochondrial contacts have a significant regulatory effect on mitochondrial transfer. Healthy DPSCs were co-cultured directly or indirectly with injured DPSCs in the first molar of 1-2 month SD rats or in vitro. Mitochondrial transfer was observed after 24 h of co-culture using fluorescence microscopy and live cell workstation. After co-culture for 1W, 8-OhdG immunofluorescence, mitochondrial membrane potential and total oxidant status/total antioxidant status were used to detect the mitochondrial function of injured DPSCs before and after mitochondrial transfer. Subsequently, mitochondria-ER co-transfer was regulated by modulating mitochondria-ER binding in healthy DPSCs, and the results of GRP78 and CHOP in DPSCs, and PDI immunofluorescence and haematoxylin and eosin staining of pulp tissue were analysed to clarify the effects of modulating mitochondria-ER co-transfer on endoplasmic reticulum stress (ERS), and on pulp injury repair. Fluorescence microscopy and live cell workstation results showed significant mitochondrial transfer between DPSCs. Meanwhile, mitochondrial transfer significantly restored mitochondrial function in injured DPSCs. By modulating mitochondrial-ER binding, the efficiency of mitochondrial transfer between DPSCs was significantly affected and had an impact on ERS in injured cells. Mitochondrial transfer of DPSCs significantly promotes pulpal injury repair and functional recovery of damaged DPSCs, and mitochondrial transfer of DPSCs is regulated by mitochondria-ER binding.
Topics: Rats; Animals; Stem Cells; Cells, Cultured; Dental Pulp; Rats, Sprague-Dawley; Stromal Cells; Endoplasmic Reticulum; Cell Differentiation; Cell Proliferation
PubMed: 37493094
DOI: 10.1111/cpr.13530 -
Zhonghua Kou Qiang Yi Xue Za Zhi =... Jan 2024Deep caries occurs when caries progresses to the deep dentin layer, and further progression has the risk of pulp exposure, which may affect pulp vitality and tooth...
Deep caries occurs when caries progresses to the deep dentin layer, and further progression has the risk of pulp exposure, which may affect pulp vitality and tooth longevity. Currently, there are no objective standards for the diagnosis of deep caries. In addition, traditional therapy for deep caries emphasizes complete debridement of the decayed tissue, resulting in an incremental high risk of pulp exposure. There are different views on how to deal with the remaining dentin after caries removal, and root canal treatment is often adopted directly after pulp exposure. In recent years, due to advances in dental pulp biology, bioactive pulp-capping materials, and clinical evidence-based medicine, the principle of deep caries treatment has shifted to pulp protection. Based on the latest international research progress, evidence-based medicine and expert consensus, we present a series of advancements in this article, including the terminology of deep caries, pathological changes and defense mechanisms of the pulp close to the deep caries, treatment principles of deep caries, technical strategies for carious tissues removal, and the decision-making of treatment protocols after pulp exposure, with the aim of enhancing the understanding of deep caries among dentists, as well as providing a reference for the clinical diagnosis and treatment of deep caries.
Topics: Humans; Dental Pulp Exposure; Dental Caries Susceptibility; Dental Pulp Capping; Root Canal Therapy; Dental Caries; Dental Pulp
PubMed: 38172058
DOI: 10.3760/cma.j.cn112144-20231018-00203 -
Journal of Endodontics Dec 2023The regeneration of pulp tissue is crucial for true regenerative endodontic treatment, which requires a reduction in osteogenic differentiation. Garcinol, a histone...
INTRODUCTION
The regeneration of pulp tissue is crucial for true regenerative endodontic treatment, which requires a reduction in osteogenic differentiation. Garcinol, a histone acetyltransferase inhibitor, is a natural regulator that is known to suppress the osteogenic differentiation of dental pulp stem cells. In this study, the inhibitory effect of garcinol on the osteogenic differentiation of human dental pulp stem cells (hDPSCs) was evaluated using three-dimensional culture under in vitro and in vivo conditions.
METHODS
hDPSCs were obtained from caries-free third molars and cultured with 10 μM garcinol for 7 days in an ultra-low attachment plate. The cell stemness and expression of osteogenic differentiation-related genes were analyzed using reverse transcription-polymerase chain reaction and single-cell analysis. A transplantation experiment was performed in mice to investigate whether garcinol-treated hDPSCs showed restrained osteogenic differentiation.
RESULTS
hDPSCs cultured in the U-shaped ultra-low attachment plate showed the highest expression of stemness-related genes. Garcinol-treated hDPSCs demonstrated downregulation of osteogenic differentiation, with lower expression of bone sialoprotein, which is related to bone formation, and higher expression of dentin sialophosphoprotein, which is related to dentin formation. However, the garcinol-treated hDPSCs did not show any alterations in their stemness. Consistent results were observed in the transplantation experiment in mice.
CONCLUSIONS
Garcinol reduced the osteogenic differentiation of hDPSCs, which can contribute to true regenerative endodontic treatment.
Topics: Humans; Animals; Mice; Osteogenesis; Dental Pulp; Stem Cells; Cell Differentiation; Cells, Cultured; Cell Proliferation
PubMed: 37657731
DOI: 10.1016/j.joen.2023.08.016 -
International Journal of Environmental... Sep 2023Type 2 diabetes mellitus (T2DM) is associated with functional deterioration of the salivary gland and dental pulp, related to oxidative stress. The aim was to integrate...
Type 2 diabetes mellitus (T2DM) is associated with functional deterioration of the salivary gland and dental pulp, related to oxidative stress. The aim was to integrate experimental and bioinformatic findings to analyze the cellular mechanism of melatonin (MEL) action in the human parotid gland and dental pulp in diabetes. Human parotid gland tissue was obtained from 16 non-diabetic and 16 diabetic participants, as well as human dental pulp from 15 non-diabetic and 15 diabetic participants. In human non-diabetic and diabetic parotid gland cells (hPGCs) as well as in dental pulp cells (hDPCs), cultured in hyper- and normoglycemic conditions, glial cell line-derived neurotrophic factor (GDNF), MEL, inducible nitric oxide synthase (iNOS) protein expression, and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA) and spectrophotometrically. Bioinformatic analysis was performed using ShinyGO (v.0.75) application. Diabetic participants had increased GDNF and decreased MEL in parotid ( < 0.01) and dental pulp ( < 0.05) tissues, associated with increased iNOS and SOD activity. Normoglycemic hDPCs and non-diabetic hPGCs treated with 0.1 mM MEL had increased GDNF ( < 0.05), while hyperglycemic hDPCs treated with 1 mM MEL showed a decrease in up-regulated GDNF ( < 0.05). Enrichment analyses showed interference with stress and ATF/CREB signaling. MEL induced the stress-protective mechanism in hyperglycemic hDPCs and diabetic hPGCs, suggesting MEL could be beneficial for diabetes-associated disturbances in oral tissues.
Topics: Humans; Parotid Gland; Diabetes Mellitus, Type 2; Glial Cell Line-Derived Neurotrophic Factor; Melatonin; Dental Pulp; Computational Biology; Superoxide Dismutase
PubMed: 37754589
DOI: 10.3390/ijerph20186727