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International Endodontic Journal May 2024This current Mendelian randomization (MR) study aims to comprehensively explore the potential bidirectional link between pulp and periapical disease (PAP) with type 2... (Meta-Analysis)
Meta-Analysis
AIM
This current Mendelian randomization (MR) study aims to comprehensively explore the potential bidirectional link between pulp and periapical disease (PAP) with type 2 diabetes mellitus (T2DM).
METHODOLOGY
Summary level data of European-based population genome-wide association studies (GWASs) were employed to undertake this MR study. With the selection of single nucleotide polymorphisms (SNPs) as the instrumental variable, the radial inverse-variance weighted (radial IVW) method with modified second-order weights was applied as the primary method. Additionally, a range of sensitivity analyses were conducted to investigate pleiotropy. Results from different sources of outcome were pooled by meta-analysis with the fixed model.
RESULTS
The results of this MR analysis did not suggest a significant impact of pulp and periapical disease on type 2 diabetes (combined OR = 1.04, 95% CI: 1.00-1.07, p = .033) and vice versa (OR = 1.04, 95% CI: 0.96-1.14, p = .329). No significant pleiotropy was detected in the final model after the removal of outliers, demonstrating the reliability of the results in our primary analysis.
CONCLUSIONS
With the limitations inherent in the present MR study, there is no significant evidence in either direction to suggest a causal association between pulp and periapical disease and type 2 diabetes mellitus.
Topics: Humans; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Dental Pulp Diseases; Periapical Diseases
PubMed: 38411530
DOI: 10.1111/iej.14034 -
Oral Diseases Sep 2023This review aimed to summarize recent progress on syndromic dentin defects, promoting a better understanding of systemic diseases with dentin malformations, the... (Review)
Review
OBJECTIVE
This review aimed to summarize recent progress on syndromic dentin defects, promoting a better understanding of systemic diseases with dentin malformations, the molecules involved, and related mechanisms.
SUBJECTS AND METHODS
References on genetic diseases with dentin malformations were obtained from various sources, including PubMed, OMIM, NCBI, and other websites. The clinical phenotypes and genetic backgrounds of these diseases were then summarized, analyzed, and compared.
RESULTS
Over 10 systemic diseases, including osteogenesis imperfecta, hypophosphatemic rickets, vitamin D-dependent rickets, familial tumoral calcinosis, Ehlers-Danlos syndrome, Schimke immuno-osseous dysplasia, hypophosphatasia, Elsahy-Waters syndrome, Singleton-Merten syndrome, odontochondrodysplasia, and microcephalic osteodysplastic primordial dwarfism type II were examined. Most of these are bone disorders, and their pathogenic genes may regulate both dentin and bone development, involving extracellular matrix, cell differentiation, and metabolism of calcium, phosphorus, and vitamin D. The phenotypes of these syndromic dentin defects various with the involved genes, part of them are similar to dentinogenesis imperfecta or dentin dysplasia, while others only present one or two types of dentin abnormalities such as discoloration, irregular enlarged or obliterated pulp and canal, or root malformation.
CONCLUSION
Some specific dentin defects associated with systemic diseases may serve as important phenotypes for dentists to diagnose. Furthermore, mechanistic studies on syndromic dentin defects may provide valuable insights into isolated dentin defects and general dentin development or mineralization.
Topics: Humans; Dentinogenesis Imperfecta; Odontodysplasia; Osteogenesis Imperfecta; Dentin; Vitamin D
PubMed: 37094075
DOI: 10.1111/odi.14589 -
Nature Reviews. Urology Dec 2023Somatic stem cells have been obtained from solid organs and tissues, including the bone marrow, placenta, corneal stroma, periosteum, adipose tissue, dental pulp and... (Review)
Review
Somatic stem cells have been obtained from solid organs and tissues, including the bone marrow, placenta, corneal stroma, periosteum, adipose tissue, dental pulp and skeletal muscle. These solid tissue-derived stem cells are often used for tissue repair, disease modelling and new drug development. In the past two decades, stem cells have also been identified in various body fluids, including urine, peripheral blood, umbilical cord blood, amniotic fluid, synovial fluid, breastmilk and menstrual blood. These body fluid-derived stem cells (BFSCs) have stemness properties comparable to those of other adult stem cells and, similarly to tissue-derived stem cells, show cell surface markers, multi-differentiation potential and immunomodulatory effects. However, BFSCs are more easily accessible through non-invasive or minimally invasive approaches than solid tissue-derived stem cells and can be isolated without enzymatic tissue digestion. Additionally, BFSCs have shown good versatility in repairing genitourinary abnormalities in preclinical models through direct differentiation or paracrine mechanisms such as pro-angiogenic, anti-apoptotic, antifibrotic, anti-oxidant and anti-inflammatory effects. However, optimization of protocols is needed to improve the efficacy and safety of BFSC therapy before therapeutic translation.
Topics: Pregnancy; Adult; Female; Humans; Mesenchymal Stem Cells; Stem Cells; Placenta; Cell Differentiation; Body Fluids
PubMed: 37414959
DOI: 10.1038/s41585-023-00787-2 -
International Endodontic Journal Oct 2023The diagnosis of the status of the inflamed pulp is essential in clinical diagnosis and treatment provision. There are a limited number of well-designed and... (Review)
Review
BACKGROUND
The diagnosis of the status of the inflamed pulp is essential in clinical diagnosis and treatment provision. There are a limited number of well-designed and well-executed clinical trials on the diagnosis of the true status of the pulp.
OBJECTIVES
Three PICO questions were formulated and agreed a priori by the European Society of Endodontology to evaluate the clinical tests for sensibility testing, determination of biomarkers and pulp bleeding with regard to their suitability to correctly diagnose the condition of the pulp tissue for the development of S3-Level guidelines.
METHODS
A literature search was conducted using PubMed, Clarivate Analytics' Web of Science, Scopus, Google Scholar and Cochrane Central Register of Controlled Trials from inception to 21 January 2022. Additionally, a hand search was performed, and the contents of the major subject journals were also examined. Eligibility criteria followed the proposed PICO questions. Two independent reviewers were involved in study selection, data extraction and appraising the included studies; disagreements were resolved by a third reviewer. The risk of bias was assessed by the QUADAS-2 tool for diagnostic accuracy studies, the Newcastle-Ottawa scale for noncomparative, nonrandomized studies and the Newcastle-Ottawa Quality Assessment scale adapted for cross-sectional studies.
RESULTS
In total, 28 studies out of 29 publications were considered eligible and were included in the review. Twelve studies were identified to investigate the diagnostic accuracy of the pulp vitality. Ten studies fulfilled the criteria to evaluate the diagnostic accuracy of the pulpal conditions, while 6 studies investigating the expression of biomarkers were eligible. Three studies addressing the prognostic factors and therapeutic interventions relating to pulpal status were included.
DISCUSSION
The core problem in pulp diagnostics is that a reliable reference standard is lacking under clinical conditions. Based on limited evidence, the most promising current approach seems to define a combination of different clinical tests and symptoms, probably in future including molecular diagnosis ("diagnostic package") will be required to ascertain the best possible strategy to clinically diagnose true pulpal conditions.
CONCLUSIONS
The effectiveness of diagnosing pulpitis is low due to limited scientific evidence regarding the accuracy and reproducibility of diagnostic tests. There is a lack of evidence to determine the true status of the pulp or to identify prognostic indicators allowing for a reliable pre-operative estimation of the outcome of vital pulp treatment.
REGISTRATION
PROSPERO database (CRD42021265366).
Topics: Humans; Pulpitis; Cross-Sectional Studies; Reproducibility of Results; Dental Pulp; Dental Pulp Diseases; Biomarkers
PubMed: 35536159
DOI: 10.1111/iej.13762 -
Primary Dental Journal Dec 2023Traumatic dental injuries pose a variety of complex ongoing issues to the dental practitioner. As dental injuries are commonly experienced at a young age, the treatment... (Review)
Review
Traumatic dental injuries pose a variety of complex ongoing issues to the dental practitioner. As dental injuries are commonly experienced at a young age, the treatment often takes place during adolescence or early in adulthood years at crucial development stages and very early in the life of the permanent successor. Therefore, the ability to correctly diagnose the injury, and follow an appropriate management plan should increase practitioners' ability to improve both the outcomes of dental trauma and long-term prognosis of the tooth.The consequences of dental trauma can be explored by taking into consideration the type of injury, which enables an assessment of the degree of insult to the pulpal tissues, neurovascular bundle, periodontal ligament and cemental cells. This has a direct influence on post-trauma complications. Early intervention, where indicated, and appropriate follow-up utilising international guidelines is imperative to identify changing diagnoses and act accordingly. This review paper will discuss the classification of traumatic injuries and their associated outcomes with management strategies for emerging disease including potential endodontic and restorative complexities and when to refer to secondary care.
Topics: Adolescent; Humans; Tooth Injuries; Dentists; Professional Role; Tooth; Dental Pulp
PubMed: 38018673
DOI: 10.1177/20501684231213908 -
Journal of Dental Research Dec 2023Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have...
Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have some limitations. For instance, RCT leads to removing significant dentin in the coronal third of the tooth that increases root-fracture risk, which forces tooth removal. The ideal therapeutic goal is dental pulp regeneration, which is not achievable with RCT. Specialized proresolving mediators (SPMs) are well known for inflammatory resolution. The resolution of inflammation and tissue restoration or regeneration is a dynamic and continuous process. SPMs not only have potent immune-modulating functions but also effectively promote tissue homeostasis and regeneration. Resolvins have been shown to promote dental pulp regeneration. The purpose of this study was to explore further the cellular target of Resolvin E1 (RvE1) therapy in dental pulp regeneration and the impact of RvE1 in infected pulps. We investigated the actions of RvE1 on experimentally exposed pulps with or without microbial infection in an ; genetically defined mouse model. Our results showed RvE1 promoted Axin2-tdTomato cell expansion and odontoblastic differentiation after direct pulp capping in the mouse, which we used to mimic reversible pulpitis cases in the clinic. In cultured mouse dental pulp stem cells (mDPSCs), RvE1 facilitated Axin2-tdTomato cell proliferation and odontoblastic differentiation and also rescued impaired functions after lipopolysaccharide stimulation. In infected pulps exposed to the oral environment for 24 h, RvE1 suppressed inflammatory infiltration, reduced bacterial invasion in root canals, and prevented the development of apical periodontitis, while its proregenerative impact was limited. Collectively, topical treatment with RvE1 facilitated dental pulp regenerative properties by promoting Axin2-expressing cell proliferation and differentiation. It also modulated the resolution of inflammation, reduced infection severity, and prevented apical periodontitis, presenting RvE1 as a novel therapeutic for treating endodontic diseases.
Topics: Mice; Animals; Pulpitis; Dental Pulp; Periapical Periodontitis; Inflammation; Bacteria; Regeneration; Axin Protein
PubMed: 37837227
DOI: 10.1177/00220345231197156 -
Graefe's Archive For Clinical and... Nov 2023Keratoconus is a corneal ectatic disease caused by stromal thinning leading to astigmatism and progressive loss of vision. Loss of the keratocytes and excessive... (Review)
Review
BACKGROUND
Keratoconus is a corneal ectatic disease caused by stromal thinning leading to astigmatism and progressive loss of vision. Loss of the keratocytes and excessive degradation of collagen fibres by matrix metalloproteinases are the molecular signatures of the disease. Despite several limitations, corneal collagen cross-linking and keratoplasty are the most widely used treatment options for keratoconus. In the pursuit of alternative treatment modalities, clinician scientists have explored cell therapy paradigms for treating the condition.
METHODS
Articles pertaining to keratoconus cell therapy with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility.
RESULTS
Various cellular abnormalities have been reported in keratoconus. Diverse cell types such as mesenchymal stromal cells, dental pulp cells, bone marrow stem cells, haematopoietic stem cells, adipose-derived stem cells apart from embryonic and induced pluripotent stem cells can be used for keratoconus cell therapy. The results obtained show that there is a potential for these cells from various sources as a viable treatment option.
CONCLUSION
There is a need for consensus with respect to the source of cells, mode of delivery, stage of disease, and duration of follow-up, to establish a standard operating protocol. This would eventually widen the cell therapy options for corneal ectatic diseases beyond keratoconus.
PubMed: 37074409
DOI: 10.1007/s00417-023-06064-7 -
Journal of Periodontal Research Aug 2023Periodontal ligament (PDL) and dental pulp (DP) share a common origin but have distinct biological and mechanical functions. To what extent the mechanoresponsive...
BACKGROUND AND OBJECTIVE
Periodontal ligament (PDL) and dental pulp (DP) share a common origin but have distinct biological and mechanical functions. To what extent the mechanoresponsive property of PDL can be attributed to its unique transcriptional profiles of cellular heterogeneity is unclear. This study aims to decipher cellular heterogeneity and distinct mechanoresponsive characteristics of odontogenic soft tissues and their underlying molecular mechanisms.
MATERIALS AND METHODS
A single-cell comparison of digested human periodontal ligament (PDL) and dental pulp (DP) was performed using scRNA-seq. An in vitro loading model was constructed to measure mechanoresponsive ability. Dual-luciferase assay, overexpression, and shRNA knockdown were used to investigate the molecular mechanism.
RESULTS
Our results demonstrate striking fibroblast heterogeneity across and within human PDL and DP. We demonstrated that a tissue-specific subset of fibroblasts existed in PDL exhibiting high expression of mechanoresponsive extracellular matrix (ECM) genes, which was verified by an in vitro loading model. ScRNA-seq analysis indicated a particularly enriched regulator in PDL-specific fibroblast subtype, Jun Dimerization Protein 2 (JDP2). Overexpression and knockdown of JDP2 extensively regulated the downstream mechanoresponsive ECM genes in human PDL cells. The force loading model demonstrated that JDP2 responded to tension and that knockdown of JDP2 effectively inhibited the mechanical force-induced ECM remodeling.
CONCLUSIONS
Our study constructed the PDL and DP ScRNA-seq atlas to demonstrate PDL and DP fibroblast cellular heterogeneity and identify a PDL-specific mechanoresponsive fibroblast subtype and its underlying mechanism.
Topics: Humans; Cells, Cultured; Single-Cell Gene Expression Analysis; Fibroblasts; Extracellular Matrix; Periodontal Ligament
PubMed: 37221903
DOI: 10.1111/jre.13139 -
Journal of Bone and Mineral Metabolism Sep 2023Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral...
INTRODUCTION
Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral density and various oral diseases, we conducted the Mendelian randomization analysis to explore the association.
MATERIALS AND METHODS
Two-sample bidirectional Mendelian analysis was used to explore the relationship between heel bone mineral density and various oral diseases. The inverse-variance weighted (IVW) was used as the primary effect estimate, and various methods were applied to test the reliability and stability of the results, namely MR-Egger, weighted median, simple mode, and weighted mode.
RESULTS
This study showed that there was a negative relationship between heel BMD and periodontitis when heel BMD was used as an exposure factor and periodontitis as an outcome factor (IVW OR = 0.85; 95% CI, 0.75-0.95; p = 0.005). Bidirectional Mendelian randomization showed that there was no statistically significant association between periodontitis and heel bone mineral density when chronic periodontitis was the exposure factor (p > 0.05). And there was no significant relationship between heel bone mineral density and other oral diseases (dental caries, diseases of pulp and periapical tissues, impacted teeth, cleft lip, and cleft palate, oral and oropharyngeal cancer) (p > 0.05).
CONCLUSION
This study showed that there was a negative relationship between heel bone density and periodontitis, and the decrease in heel bone density could promote the occurrence of periodontitis. In addition, there was no statistically significant relationship between heel bone density and other oral diseases.
Topics: Humans; Bone Density; Dental Caries; Mendelian Randomization Analysis; Reproducibility of Results; Fractures, Bone; Polymorphism, Single Nucleotide
PubMed: 37507596
DOI: 10.1007/s00774-023-01443-w