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International Dental Journal Apr 2024In recent years, the field of regenerative dentistry has garnered considerable attention for its focus on restoring and renewing damaged dental tissue. This narrative... (Review)
Review
In recent years, the field of regenerative dentistry has garnered considerable attention for its focus on restoring and renewing damaged dental tissue. This narrative review explores the potential of bone morphogenetic protein 7 (BMP7) and its diverse applications in the regeneration of dental tissue. Recently, significant efforts have been made to understand BMP7's role in advancing regenerative dentistry. Amongst the various signalling molecules investigated for their regenerative capabilities, BMP7 emerges as a pivotal candidate, demonstrating the ability to stimulate the regeneration of dental pulp, periodontal, craniofacial, and alveolar bone tissues for dental implant placement. Whilst BMP7 exhibits significant promise as a therapeutic agent in regenerative dentistry, further research and clinical trials are necessary to fully unlock its potential and optimise its clinical effectiveness in addressing diverse dental and craniofacial conditions. This review highlights BMP7's substantial potential and emphasises the ongoing need for continued research to effectively harness its clinical utility in diverse dental and craniofacial contexts.
PubMed: 38664175
DOI: 10.1016/j.identj.2024.04.002 -
Human Genomics Oct 2023Tooth agenesis is a common dental anomaly that can substantially affect both the ability to chew and the esthetic appearance of patients. This study aims to identify...
BACKGROUND
Tooth agenesis is a common dental anomaly that can substantially affect both the ability to chew and the esthetic appearance of patients. This study aims to identify possible genetic factors that underlie various forms of tooth agenesis and to investigate the possible molecular mechanisms through which human dental pulp stem cells may play a role in this condition.
RESULTS
Using whole-exome sequencing of a Han Chinese family with non-syndromic tooth agenesis, a rare mutation in FGFR1 (NM_001174063.2: c.103G > A, p.Gly35Arg) was identified as causative and confirmed by Sanger sequencing. Via GeneMatcher, another family with a known variant (NM_001174063.2: c.1859G > A, p.Arg620Gln) was identified and diagnosed with tooth agenesis and a rare genetic disorder with considerable intrafamilial variability. Fgfr1 is enriched in the ectoderm during early embryonic development of mice and showed sustained low expression during normal embryonic development of Xenopus laevis frogs. Functional studies of the highly conserved missense variant c.103G > A showed deleterious effects. FGFR1 (c.103G > A) was overexpressed compared to wildtype and promoted proliferation while inhibiting apoptosis in HEK293 and human dental pulp stem cells. Moreover, the c.103G > A variant was found to suppress the epithelial-mesenchymal transition. The variant could downregulate ID4 expression and deactivate the TGF-beta signaling pathway by promoting the expression of SMAD6 and SMAD7.
CONCLUSION
Our research broadens the mutation spectrum associated with tooth agenesis and enhances understanding of the underlying disease mechanisms of this condition.
Topics: Humans; HEK293 Cells; Anodontia; Mutation; Mutation, Missense; Receptor, Fibroblast Growth Factor, Type 1
PubMed: 37833774
DOI: 10.1186/s40246-023-00539-8 -
Translational Stroke Research Oct 2023Aneurysmal subarachnoid hemorrhage (SAH) can cause severe neurological deficits and high mortality. Early brain edema following SAH contributes to the initiation of...
Dental Pulp Stem Cell-Derived Conditioned Medium Alleviates Subarachnoid Hemorrhage-Induced Microcirculation Impairment by Promoting M2 Microglia Polarization and Reducing Astrocyte Swelling.
Aneurysmal subarachnoid hemorrhage (SAH) can cause severe neurological deficits and high mortality. Early brain edema following SAH contributes to the initiation of microcirculation impairment and may further lead to delayed ischemic neurologic deficit (DIND). This study aimed to investigate whether dental pulp stem cell conditioned medium (DPSC-CM) ameliorates SAH-induced microcirculation impairment and the underlying mechanisms. SAH was induced via intrathecal injection of fresh autologous blood in Wistar male adult rat. DPSC-CM or DPSC-CM + insulin growth factor-1 (IGF-1) antibody was randomly administered by intrathecal route 5 min after SAH induction. To evaluate the underlying mechanisms of DPSC-CM in the treatment of SAH, primary rat astrocyte and microglia co-cultures were challenged with hemolysate or SAH-patient CSF in the presence or absence of DPSC-CM. The results showed that in vivo, DPSC-CM treatment decreased the brain water content, improved microcirculation impairment and enhanced functional recovery at 24 h post-SAH. DPSC-CM treatment also alleviated the expressions of water channel protein aquaporin-4 (AQP4) and pro-inflammatory cytokines, and enhanced the expressions of anti-inflammatory factors in the cortical region. However, all the beneficial effects of DPSC-CM were abrogated after treatment with IGF-1 neutralizing antibody. The in vitro results further showed that DPSC-CM treatment reduced hemolysate/SAH-patient CSF-induced astrocyte swelling and promoted M2 microglia polarization, partially through IGF-1/AKT signaling. The data suggested that DPSC-CM significantly reduced brain edema and rescued microcirculation impairment with concomitant anti-inflammatory benefits after SAH, and may potentially be developed into a novel therapeutic strategy for SAH.
Topics: Rats; Male; Animals; Microglia; Rats, Wistar; Subarachnoid Hemorrhage; Culture Media, Conditioned; Disease Models, Animal; Brain Edema; Microcirculation; Astrocytes; Insulin-Like Growth Factor I; Dental Pulp; Anti-Inflammatory Agents; Stem Cells
PubMed: 36181630
DOI: 10.1007/s12975-022-01083-8 -
Neural Regeneration Research May 2024Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury. However, whether the human dental pulp stem...
Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury. However, whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear. In the present study, we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells. We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury, decreased expression of the microglial pyroptosis markers NLRP3, GSDMD, caspase-1, and interleukin-1β, promoted axonal and myelin regeneration, and inhibited the formation of glial scars. In addition, in a lipopolysaccharide-induced BV2 microglia model, conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1β pathway. These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1β pathway, thereby promoting the recovery of neurological function after spinal cord injury. Therefore, conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.
PubMed: 37862215
DOI: 10.4103/1673-5374.385309 -
Journal of Translational Medicine Oct 2023Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug...
BACKGROUND
Systemic administration of oncolytic adenovirus for cancer therapy is still a challenge. Mesenchymal stem cells as cell carriers have gained increasing attention in drug delivery due to their excellent tumor tropism, immunosuppressive modulatory effects, and paracrine effects. However, the potential of human dental pulp stem cells (hDPSCs) loaded with oncolytic adenovirus for cancer biotherapy has not been investigated yet.
METHODS
The stemness of hDPSCs was characterized by FACS analysis and Alizarin red staining, Oil Red O staining, and immunofluorescence assays. The biological fitness of hDPSCs loaded with oncolytic adenovirus YSCH-01 was confirmed by virus infection with different dosages and cell viability CCK-8 assays. Additionally, the expression of CAR receptor in hDPSCs was detected by qPCR assay. Tumor tropism of hDPSC loaded with YSCH-01 in vitro and in vivo was investigated by Transwell assays and living tumor-bearing mice imaging technology and immunohistochemistry, Panoramic scanning of frozen section slices assay analysis. Furthermore, the antitumor efficacy was observed through the different routes of YSCH-01/hPDSCs administration in SW780 and SCC152 xenograft models. The direct tumor cell-killing effect of YSCH-01/hDPSCs in the co-culture system was studied, and the supernatant of YSCH-01/hDPSCs inhibited cell growth was further analyzed by CCK-8 assays.
RESULTS
hDPSCs were found to be susceptible to infection by a novel oncolytic adenovirus named YSCH-01 and were capable of transporting this virus to tumor sites at 1000 VP/cell infectious dosage in vitro and in vivo. Moreover, it was discovered that intraperitoneal injection of hDPSCs loaded with oncolytic adenovirus YSCH-01 exhibited potential anti-tumor effects in both SW780 and SCC152 xenograft models. The crucial role played by the supernatant secretome derived from hDPSCs loaded with YSCH-01 significantly exerted a specific anti-tumor effect without toxicity for normal cells, in both an active oncolytic virus and an exogenous protein-independent manner. Furthermore, the use of hDPSCs as a cell carrier significantly reduced the required dosage of virus delivery in vivo compared to other methods.
CONCLUSIONS
These findings highlight the promising clinical potential of hDPSCs as a novel cell carrier in the field of oncolytic virus-based anti-cancer therapy.
Topics: Humans; Mice; Animals; Adenoviridae; Dental Pulp; Sincalide; Oncolytic Viruses; Oncolytic Virotherapy; Mesenchymal Stem Cells; Xenograft Model Antitumor Assays
PubMed: 37789452
DOI: 10.1186/s12967-023-04539-z -
Improved Method for Dental Pulp Stem Cell Preservation and Its Underlying Cell Biological Mechanism.Cells Aug 2023Dental pulp stem cells (DPSCs) are considered a valuable cell source for regenerative medicine because of their high proliferative potential, multipotency, and...
Dental pulp stem cells (DPSCs) are considered a valuable cell source for regenerative medicine because of their high proliferative potential, multipotency, and availability. We established a new cryopreservation method (NCM) for collecting DPSCs, in which the tissue itself is cryopreserved and DPSCs are collected after thawing. We improved the NCM and developed a new method for collecting and preserving DPSCs more efficiently. Dental pulp tissue was collected from an extracted tooth, divided into two pieces, sandwiched from above and below using cell culture inserts, and cultured. As a result, the cells in the pulp tissue migrated vertically over time and localized near the upper and lower membranes over 2-3 days. With regard to the underlying molecular mechanism, SDF1 was predominantly involved in cell migration. This improved method is valuable and enables the more efficient collection and reliable preservation of DPSCs. It has the potential to procure a large number of DPSCs stably.
Topics: Dental Pulp; Cryopreservation; Cancer Vaccines; Cell Culture Techniques; Stem Cells
PubMed: 37681870
DOI: 10.3390/cells12172138 -
BMC Oral Health Nov 2023N6-methyladenosine (mA) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development...
BACKGROUND
N6-methyladenosine (mA) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development of diseases. However, their significance in pulpitis remains largely unknown. Here, we sought to identify and validate the mA RNA regulatory network in pulpitis.
METHODS
Gene expression data for mA regulators in human pulpitis and normal pulp tissues from public GEO databases were analyzed. Bioinformatics analysis including Gene ontology (GO) functional, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed by R package, and Cytoscape software was used to study the role of mA miRNA-mRNA regulatory network in pulpitis. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of key mA regulators in collected human pulpitis specimens.
RESULTS
Differential genes between pulpitis and normal groups were found from the GEO database, and further analysis found that there were significant differences in the mA modification-related genes ALKBH5, METTL14, METTL3, METTL16, RBM15B and YTHDF1. And their interaction relationships and hub genes were determined. The hub m6A regulator targets were enriched in immune cells differentiation, glutamatergic synapse, ephrin receptor binding and osteoclast differentiation in pulpitis. Validation by qRT-PCR showed that the expression of methylases METTL14 and METTL3 was decreased, thus these two genes may play a key role in pulpitis.
CONCLUSION
Our study identified and validated the mA RNA regulatory network in pulpitis. These findings will provide valuable resource to guide the mechanistic and therapeutic analysis of the role of key mA modulators in pulpitis.
Topics: Humans; Pulpitis; MicroRNAs; RNA, Messenger; Dental Pulp; Computational Biology; Methyltransferases
PubMed: 37978362
DOI: 10.1186/s12903-023-03578-8 -
The Libyan Journal of Medicine Dec 2024The study aimed to radiographically assess the characteristics of pulp stones (PS) and pulp canal obliteration (PCO) in teeth and examined their associations with... (Observational Study)
Observational Study
The study aimed to radiographically assess the characteristics of pulp stones (PS) and pulp canal obliteration (PCO) in teeth and examined their associations with various dental parameters such as caries, restorations, periodontal status, and age. This cross-sectional observational study was conducted at the Faculty of Dentistry, King Abdulaziz University between September 2022, and May 2023, involved 101 patients exhibiting 402 teeth with PS or PCO. Data were collected from periapical and bitewing radiographs, and analyzed by two calibrated dentists. Multiple dental parameters were assessed, including caries level, presence and level of restorations, periodontal condition, and age of the patient. The study population consisted of 62 females and 39 males, with an age range of 18-65 years. Inter- and intra-examiner reliability were high (Kappa = 0.88 and 0.98 respectively). PS were more commonly found in molars (81.2%), while PCO were presented in only 115 teeth (23%). Age significantly affected the type of calcification ( < 0.001), with PS more common in the 20-30 age group and PCO more common in individuals over 40. Presence of caries was significantly associated with the type of calcification ( = 0.013), but restoration was not. The majority of teeth with PS (76%) or PCO (93%) had healthy periodontium. Around 40% of teeth with PCO showed signs of periapical changes, a finding significantly different from those with PS ( < 0.001). Pulp calcifications were significantly associated with various dental parameters, including caries presence, age, and periodontal status. The findings provide crucial insights into the epidemiology and aetiology of pulp calcifications.
Topics: Female; Male; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Cross-Sectional Studies; Dental Pulp Calcification; Dental Pulp Cavity; Reproducibility of Results
PubMed: 38258544
DOI: 10.1080/19932820.2024.2306768 -
Journal of Endodontics Dec 2023Osteolectin is a secreted glycoprotein of the C-type lectin domain superfamily, expressed in bone tissues and is reported as a novel osteogenic factor that promotes bone...
INTRODUCTION
Osteolectin is a secreted glycoprotein of the C-type lectin domain superfamily, expressed in bone tissues and is reported as a novel osteogenic factor that promotes bone regeneration. However, the effect of osteolectin on human dental pulp cells (hDPCs) has not been reported. Therefore, we aimed to investigate the odontoblastic differentiation of osteolectin in hDPCs and further attempt to reveal its underlying mechanism.
METHODS
Cytotoxicity assays were used to detect the cytotoxicity of osteolectin. The odontoblastic differentiation of hDPCs and its underlying mechanisms were measured by the alkaline phosphatase (ALP) activity, mineralized spots formation, and the gene and protein expression of odontoblastic differentiation through ALP staining, Alizarin red S staining, quantitative real-time polymerase chain reaction, and Western blot analysis, respectively.
RESULTS
WST-1 assay showed osteolectin at concentrations below 300 ng/ml was noncytotoxic and safe for hDPCs. The following experiment demonstrated that osteolectin could increase ALP activity, accelerate the mineralization process, and up-regulate the odontogenic differentiation markers in both gene and protein levels (P < .05). Osteolectin stimulated the phosphorylation of ERK, JNK, and Protein kinase B (AKT) in hDPCs. Extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and AKT inhibitors decreased ALP activity and mineralization capacity and suppressed the expression of dentin sialophosphoprotein and dentin matrix protein-1.
CONCLUSION
Osteolectin can promote odontoblastic differentiation of hDPCs, and the whole process may stimulate ERK, JNK, and AKT signaling pathways by increasing p-ERK, p-JNK, and p-AKT signals.
Topics: Humans; Proto-Oncogene Proteins c-akt; Extracellular Matrix Proteins; Dental Pulp; Cell Differentiation; Signal Transduction; Odontoblasts; Alkaline Phosphatase; Cells, Cultured; Cell Proliferation; Phosphoproteins
PubMed: 37774945
DOI: 10.1016/j.joen.2023.09.010 -
Biomolecules Mar 2024Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not... (Review)
Review
Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.
Topics: Regenerative Endodontics; Exosomes; Dental Pulp; Regeneration; Regenerative Medicine
PubMed: 38540750
DOI: 10.3390/biom14030330