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Saudi Medical Journal Dec 2015Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of... (Review)
Review
Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors.
Topics: Dental Pulp; Humans; Periodontal Diseases; Regeneration; Stem Cells; Tissue Engineering
PubMed: 26620980
DOI: 10.15537/smj.2015.12.12750 -
Molecules (Basel, Switzerland) Sep 2021Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral...
BACKGROUND
Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis. The impact and effects of these secretory factors on cancer cells must be understood in order to ensure their safe application in cancer patients.
OBJECTIVE
We aimed to quantify the growth factors and cytokines in DPMSC-S and assess their effect on oral cancer cell proliferation.
MATERIALS AND METHODS
DPMSCs were isolated from patients with healthy teeth ( = 5) that were indicated for extraction for orthodontic reasons. The cells were characterized using flow cytometry and conditioned medium (DPMSC-CM) was prepared. DPMSC-CM was subjected to a bead-based array to quantify the growth factors and cytokines that may affect oral carcinogenesis. The effect of DPMSC-CM (20%, 50%, 100%) on the proliferation of oral cancer cells (AW123516) was evaluated using a Ki-67-based assay at 48 h. AW13516 cultured in the standard growth medium acted as the control.
RESULTS
VEGF, HCF, Ang-2, TGF-α, EPO, SCF, FGF, and PDGF-BB were the growth factors with the highest levels in the DPMSC-CM. The highest measured pro-inflammatory cytokine was TNF-α, followed by CXCL8. The most prevalent anti-inflammatory cytokine in the DPMSC-CM was IL-10, followed by TGF-β1 and IL-4. Concentrations of 50% and 100% DPMSC-CM inhibited Ki-67 expression in AW13516, although the effect was non-significant. Moreover, 20% DPMSC-CM significantly increased Ki-67 expression compared to the control.
CONCLUSIONS
The increased Ki-67 expression of oral cancer cells in response to 20% DPMSC-CM indicates the potential for cancer progression. Further research is needed to identify their effects on other carcinogenic properties, including apoptosis, stemness, migration, invasion, adhesion, and therapeutic resistance.
Topics: Adolescent; Cell Line, Tumor; Cell Proliferation; Cell Separation; Culture Media, Conditioned; Cytokines; Dental Pulp; Humans; Intercellular Signaling Peptides and Proteins; Mesenchymal Stem Cells; Mouth Neoplasms; Primary Cell Culture; Young Adult
PubMed: 34577154
DOI: 10.3390/molecules26185683 -
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 -
Mediators of Inflammation 2015Pathogen recognition receptors (PRRs) are a class of germ line-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs). The activation of PRRs is... (Review)
Review
Pathogen recognition receptors (PRRs) are a class of germ line-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs). The activation of PRRs is crucial for the initiation of innate immunity, which plays a key role in first-line defense until more specific adaptive immunity is developed. PRRs differ in the signaling cascades and host responses activated by their engagement and in their tissue distribution. Currently identified PRR families are the Toll-like receptors (TLRs), the C-type lectin receptors (CLRs), the nucleotide-binding oligomerization domain-like receptors (NLRs), the retinoic acid-inducible gene-I-like receptors (RLRs), and the AIM2-like receptor (ALR). The environment of the dental pulp is substantially different from that of other tissues of the body. Dental pulp resides in a low compliance root canal system that limits the expansion of pulpal tissues during inflammatory processes. An understanding of the PRRs in dental pulp is important for immunomodulation and hence for developing therapeutic targets in the field of endodontics. Here we comprehensively review recent finding on the PRRs and the mechanisms by which innate immunity is activated. We focus on the PRRs expressed on dental pulp and periapical tissues and their role in dental pulp inflammation.
Topics: Animals; Carrier Proteins; Dental Pulp; Humans; Immunity, Innate; Lectins, C-Type; NLR Family, Pyrin Domain-Containing 3 Protein; Nod1 Signaling Adaptor Protein; Nod2 Signaling Adaptor Protein; Receptors, Pattern Recognition; Toll-Like Receptors
PubMed: 26576076
DOI: 10.1155/2015/794143 -
Experimental Cell Research Jul 2020Mineralization disorders with a broad range of etiological factors represent a huge challenge in dental diagnosis and therapy. Hypophosphatasia (HPP) belongs to the rare...
Mineralization disorders with a broad range of etiological factors represent a huge challenge in dental diagnosis and therapy. Hypophosphatasia (HPP) belongs to the rare diseases affecting predominantly mineralized tissues, bones and teeth, and occurs due to mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNAP). Here we analyzed stem cells from bone marrow (BMSCs), dental pulp (DPSCs) and periodontal ligament (PDLSCs) in the absence and presence of efficient TNAP inhibitors. The differentiation capacity, expression of surface markers, and gene expression patterns of donor-matched dental cells were compared during this in vitro study. Differentiation assays showed efficient osteogenic but low adipogenic differentiation (aD) capacity of PDLSCs and DPSCs. TNAP inhibitor treatment completely abolished the mineralization process during osteogenic differentiation (oD). RNA-seq analysis in PDLSCs, comparing oD with and without TNAP inhibitor levamisole, showed clustered regulation of candidate molecular mechanisms that putatively impaired osteogenesis and mineralization, disequilibrated ECM production and turnover, and propagated inflammation. Combined alteration of cementum formation, mineralization, and elastic attachment of teeth to cementum via elastic fibers may explain dental key problems in HPP. Using this in vitro model of TNAP deficiency in DPSCs and PDLSCs, we provide novel putative target areas for research on molecular cues for specific dental problems in HPP.
Topics: Adolescent; Adult; Antirheumatic Agents; Biomarkers; Case-Control Studies; Cell Differentiation; Cells, Cultured; Dental Pulp; Female; Humans; Hypophosphatasia; Inflammation; Levamisole; Male; Mesenchymal Stem Cells; Osteogenesis; Periodontal Ligament; RNA-Seq; Stomatognathic Diseases; Transcriptome; Young Adult
PubMed: 32333908
DOI: 10.1016/j.yexcr.2020.112026 -
Cells Jan 2020Dental pulp plays an important role in the health of teeth. The aging of teeth is strongly related to the senescence of dental pulp cells. A novel adipokine, visfatin,...
Dental pulp plays an important role in the health of teeth. The aging of teeth is strongly related to the senescence of dental pulp cells. A novel adipokine, visfatin, is closely associated with cellular senescence. However, little is known about the effect of visfatin on the senescence of human dental pulp cells (hDPCs). Here, it was found that in vivo visfatin levels in human dental pulp tissues increase with age and are upregulated in vitro in hDPCs during premature senescence activated by HO, suggesting a correlation between visfatin and senescence. In addition, visfatin knockdown by small interfering RNA led to the reduction in hDPC senescence; however, treatment with exogenous visfatin protein induced the senescence of hDPCs along with increased NADPH consumption, which was reversed by FK866, a chemical inhibitor of visfatin. Furthermore, visfatin-induced senescence was associated with both the induction of telomere damage and the upregulation of senescence-associated secretory phenotype (SASP) factors as well as NF-κB activation, which were all inhibited by FK866. Taken together, these results demonstrate, for the first time, that visfatin plays a pivotal role in hDPC senescence in association with telomere dysfunction and the induction of SASP factors.
Topics: Adult; Cells, Cultured; Cellular Senescence; Cytokines; Dental Pulp; Female; Humans; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Young Adult
PubMed: 31940881
DOI: 10.3390/cells9010193 -
PloS One 2017Chemical decomposition and fragmentation may limit the detection of ancient host and microbial DNA while some proteins can be detected for extended periods of time. We...
Chemical decomposition and fragmentation may limit the detection of ancient host and microbial DNA while some proteins can be detected for extended periods of time. We applied paleoproteomics on 300-year-old dental pulp specimens recovered from 16 individuals in two archeological funeral sites in France, comprising one documented plague site and one documented plague-negative site. The dental pulp paleoproteome of the 16 teeth comprised 439 peptides representative of 30 proteins of human origin and 211 peptides representative of 27 proteins of non-human origin. Human proteins consisted of conjunctive tissue and blood proteins including IgA immunoglobulins. Four peptides were indicative of three presumable Yersinia pestis proteins detected in 3/8 dental pulp specimens from the plague-positive site but not in the eight dental pulp specimens collected in the plague-negative site. Paleoproteomics applied to the dental pulp is a new and innovative approach to screen ancient individuals for the detection of blood-borne pathogens and host inflammatory response.
Topics: Bacterial Proteins; Burial; Chromatography, Liquid; Dental Pulp; France; Host-Pathogen Interactions; Humans; Paleopathology; Peptides; Plague; Proteomics; Tandem Mass Spectrometry; Time Factors; Yersinia pestis
PubMed: 28746380
DOI: 10.1371/journal.pone.0180552 -
Stem Cell Research & Therapy Jan 2016Amelogenin is an extracellular matrix protein well known for its role in the organization and mineralization of enamel. Clinically, it is used for periodontal...
BACKGROUND
Amelogenin is an extracellular matrix protein well known for its role in the organization and mineralization of enamel. Clinically, it is used for periodontal regeneration and, due to its finding also in predentin and intercellular spaces of dental pulp cells, it has recently been suggested for pulp capping procedures. The aim of this study was to analyse in vitro the effect of the recombinant human full-length amelogenin on the growth and differentiation of human dental pulp stem cells (hDPSCs).
METHODS
Human DPSCs were treated with a supplement of amelogenin at a concentration of 10 ng/ml, 100 ng/ml and 1000 ng/ml. The groups were compared to the unstimulated control in terms of cell morphology and proliferation, mineralization and gene expression for ALP (alkaline phosphatase), DMP1 (dentin matrix protein-1) and DSPP (dentin sialophosphoprotein).
RESULTS
Amelogenin affects hDPSCs differently than PDL (periodontal ligament) cells and other cell lines. The proliferation rate at two weeks is significantly reduced in presence of the highest concentration of amelogenin as compared to the unstimulated control. hDPSCs treated with low concentrations present a downregulation of DMP1 and DSPP, which is significant for DSPP (p = 0.011), but not for DMP1 (p = 0.395).
CONCLUSIONS
These finding suggest that the role of full-length amelogenin is not restricted to participation in tooth structure. It influences the differentiation of hDPSC according to various concentrations and this might impair the clinical results of pulp capping.
Topics: Adult Stem Cells; Amelogenin; Biomarkers; Cell Differentiation; Cell Proliferation; Cell Shape; Cells, Cultured; Dental Pulp; Gene Expression; Humans; Odontogenesis; Regeneration
PubMed: 26762641
DOI: 10.1186/s13287-015-0269-9 -
International Journal of Molecular... Dec 2020Recently a greater interest in tissue engineering for the treatment of large bone defect has been reported. The aim of the present systematic review and meta-analysis... (Review)
Review
BACKGROUND
Recently a greater interest in tissue engineering for the treatment of large bone defect has been reported. The aim of the present systematic review and meta-analysis was to investigate the effectiveness of dental pulp stem cells and synthetic block complexes for bone defect treatment in preclinical in vivo articles.
METHODS
The electronic database and manual search was conducted on Pubmed, Scopus, and EMBASE. The papers identified were submitted for risk-of-bias assessment and classified according to new bone formation, bone graft characteristics, dental pulp stem cells (DPSCs) culture passages and amount of experimental data. The meta-analysis assessment was conducted to assess new bone formation in test sites with DPSCs/synthetic blocks vs. synthetic block alone.
RESULTS
The database search identified a total of 348 papers. After the initial screening, 30 studies were included, according to the different animal models: 19 papers on rats, 3 articles on rabbits, 2 manuscripts on sheep and 4 papers on swine. The meta-analysis evaluation showed a significantly increase in new bone formation in favor of DPSCs/synthetic scaffold complexes, if compared to the control at 4 weeks (Mean Diff: 17.09%, 95% CI: 15.16-18.91%, < 0.01) and at 8 weeks (Mean Diff: 14.86%, 95% CI: 1.82-27.91%, < 0.01) in rats calvaria bone defects.
CONCLUSION
The synthetic scaffolds in association of DPSCs used for the treatment of bone defects showed encouraging results of early new bone formation in preclinical animal studies and could represent a useful resource for regenerative bone augmentation procedures.
Topics: Animals; Bone Diseases; Bone Regeneration; Cell Differentiation; Dental Pulp; Humans; Stem Cells; Tissue Engineering; Tissue Scaffolds
PubMed: 33371390
DOI: 10.3390/ijms21249765 -
Cells Nov 2022This study aimed to explore the role of LncKCNQ1OT1/hsa-miR-153-3p/RUNX2 in the odontoblastic differentiation of human dental pulp stem cells (DPSCs) and its possible...
This study aimed to explore the role of LncKCNQ1OT1/hsa-miR-153-3p/RUNX2 in the odontoblastic differentiation of human dental pulp stem cells (DPSCs) and its possible mechanism. The expression of LncKCNQ1OT1, hsa-miR-153-3p, and RUNX2 in the odontoblastic differentiation was detected by qRT-PCR. Interaction between LncKCNQ1OT1 and hsa-miR-153-3p and interaction between hsa-miR-153-3p and RUNX2 were detected by dual-luciferase assay. The cell viability of DPSCs was detected by CCK-8, and the effect of LncKCNQ1OT1 and hsa-miR-153-3p on the odontoblastic differentiation of DPSCs was observed by alizarin red staining, alkaline phosphatase (ALP) activity assay, and Western blot for RUNX2, DSPP, and DMP-1. The results showed, during odontoblastic differentiation of DPSCs, the expression of LncKCNQ1OT1 increased, hsa-miR-153-3p expression decreased, and RUNX2 expression increased. Dual-luciferase assay showed that LncKCNQ1OT1 sponges hsa-miR-153-3p and hsa-miR-153-3p targets on RUNX2. After LncKCNQ1OT1 and hsa-miR-153-3p expressions of DPSCs were changed, the cell viability was not notably changed, but the odontoblastic differentiation was notably changed, which was confirmed with Alizarin Red staining, ALP activity, and Western blot for RUNX2, DSPP, and DMP-1. The results indicate that LncKCNQ1OT1 promotes the odontoblastic differentiation of DPSCs via regulating hsa-miR-153-3p/RUNX2 axis, which may provide a therapeutic clue for odontogenesis.
Topics: Humans; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Dental Pulp; Stem Cells
PubMed: 36359902
DOI: 10.3390/cells11213506