A novel bio-active adhesive monomer induces odontoblast differentiation: a comparative study
01 Oct 2020-International Endodontic Journal (John Wiley & Sons, Ltd)-Vol. 53, Iss: 10, pp 1413-1429
TL;DR: The novel bio-active monomer CMET had the lowest cytotoxicity among all groups and it induced the proliferation, mineralization and differentiation of odontoblast-like cells under appropriate concentrations.
Abstract: AIM To evaluate the in vitro effect of the novel adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate (4-MET), on the proliferation, mineralization and differentiation of odontoblast-like cells, comparing with 4-MET, calcium hydroxide (CH) and mineral trioxide aggregate (MTA). METHODOLOGY Rat odontoblast-like MDPC-23 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% foetal bovine serum. The powder of four tested materials (CMET, 4-MET, CH and MTA) was first dissolved in distilled water (dH2O) and then was diluted by DMEM to yield final concentrations. Solvent (dH2O) was used as a control. Cell viability was assessed using CCK-8 assay. Real-time RT-PCR was used to quantify the mRNA expression of odontogenic markers, cytokines and integrins. Mineralization inducing capacity was evaluated by alkaline phosphatase (ALPase) activity and alizarin red S staining. Statistical analyses were performed using one-way anova and post hoc Tukey's HSD test, with the significance level at 1%. RESULTS Cell viability was significantly greater in the CMET- (83 to 828 mmol L-1), CH- and MTA-treated (low concentrations) groups than that in the control group (P < 0.01). Higher concentrations of each material decreased the viable cells to different extents (P < 0.01). CMET treatment augmented the expression of several integrin subunits and exhibited the highest mRNA expression levels of odontogenic markers among all groups (P < 0.01). CH and MTA treatment caused significantly greater upregulation of pro-inflammatory cytokines expression than the other groups (P < 0.01). The calcific deposition of MDPC-23 cells was dose-dependently accelerated by the addition of CMET (P < 0.01); the enhancement of mineralization was also found in the fresh prepared CH and MTA treatments. Besides, CMET showed consistency in mineralization induction after 8 weeks storage. Exposure to SB202190, a specific p38 mitogen-activated protein kinases inhibitor, significantly decreased the ALPase activity as well as the mineral deposition which was enhanced by CMET treatment (P < 0.01). CONCLUSIONS The novel bio-active monomer had the lowest cytotoxicity among all groups and it induced the proliferation, mineralization and differentiation of odontoblast-like cells under appropriate concentrations. This adhesive monomer possesses excellent biocompatibility and hence exhibits great potential in dentine regeneration.
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TL;DR: In this article, the authors evaluated the in vitro effect of the novel bioactive adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate acid (4-MET), on human dental pulp stem cells (hDPSCs) and its capacity to induce tertiary dentin formation in a rat pulp injury model.
Abstract: This study aimed to evaluate the in vitro effect of the novel bioactive adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate acid (4-MET), on human dental pulp stem cells (hDPSCs) and its capacity to induce tertiary dentin formation in a rat pulp injury model. Aqueous solutions of four tested materials [4-MET, CMET, Ca(OH)2, and mineral trioxide aggregate (MTA)] were added to the culture medium upon confluence, and solvent (dH2O) was used as a control. Cell proliferation was assessed using the Cell Counting Kit-8 assay, and cell differentiation was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. The mineralization-inducing capacity was evaluated using alizarin red S staining and an alkaline phosphatase activity assay. For an in vivo experiment, a mechanical pulp exposure model was prepared on Wistar rats; damaged pulp was capped with Ca(OH)2 or CMET. Cavities were sealed with composite resin, and specimens were assessed after 14 and 28 days. The in vitro results showed that CMET exhibited the lowest cytotoxicity and highest odontogenic differentiation capacity among all tested materials. The favorable outcome on cell mineralization after treatment with CMET involved p38 and c-Jun N-terminal kinases signaling. The nuclear factor kappa B pathway was involved in the CMET-induced mRNA expression of odontogenic markers. Similar to Ca(OH)2, CMET produced a continuous hard tissue bridge at the pulp exposure site, but treatment with only CMET produced a regular dentinal tubule pattern. The findings suggest that (1) the evaluated novel bioactive adhesive monomer provides favorable biocompatibility and odontogenic induction capacity and that (2) CMET might be a very promising adjunctive for pulp-capping materials.
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TL;DR: The significantly higher adhesion rate of the desensitizer containing C-MET and MDCP indicated that the novel monomer contributed to the improvement in the adhesion ability.
Abstract: Recently, the development of dental materials has increased the availability of various hyperesthesia desensitizers. However, there are no studies on the duration of retreatment in terms of adherence rates. Thus, the adhesion rates of resin-based desensitizers were investigated. We used a conventional desensitizer and a recently developed desensitizer containing calcium salt of 4-methacryloxyethyl trimellitic acid (C-MET) and 10-methacryloyloxydecyl dihydrogen calcium phosphate (MDCP). These colored agents were applied to the surfaces of premolars and molars, and the area was measured from weekly oral photographs. Areas were statistically analyzed and mean values were calculated using 95% confidence intervals. A p-value of <0.05 was considered statistically significant. These rates were significantly higher on the buccal side of the maxilla and lower on the lingual side of the maxilla. In addition, the desensitizer containing C-MET and MDCP displayed significantly higher adhesion rates. It is suggested that this will require monthly follow-ups and reevaluation because both agents cause less than 10% adherence and there is almost no sealing effect after 4 weeks. In addition, the significantly higher adhesion rate of the desensitizer containing C-MET and MDCP indicated that the novel monomer contributed to the improvement in the adhesion ability.
References
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TL;DR: Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted and particular emphasis is on ERK1/2.
Abstract: Mitogen-activated protein (MAP) kinases comprise a family of ubiquitous proline-directed, protein-serine/threonine kinases, which participate in signal transduction pathways that control intracellular events including acute responses to hormones and major developmental changes in organisms. MAP kinases lie in protein kinase cascades. This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2.
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TL;DR: MTA is a promising material for root-end filling, perforation repair, vital pulp therapy, and apical barrier formation for teeth with necrotic pulps and open apexes and appears to be the material of choice for some clinical applications.
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TL;DR: Besides self-etching dentin, specific functional monomers have additional chemical bonding efficacy that is expected to contribute to their adhesive potential to tooth tissue.
Abstract: Mild self-etch adhesives demineralize dentin only partially, leaving hydroxyapatite around collagen within a submicron hybrid layer. We hypothesized that this residual hydroxyapatite may serve as a receptor for chemical interaction with the functional monomer and, subsequently, contribute to adhesive performance in addition to micro-mechanical hybridization. We therefore chemically characterized the adhesive interaction of 3 functional monomers with synthetic hydroxyapatite, using x-ray photoelectron spectroscopy and atomic absorption spectrophotometry. We further characterized their interaction with dentin ultra-morphologically, using transmission electron microscopy. The monomer 10-methacryloxydecyl dihydrogen phosphate (10-MDP) readily adhered to hydroxyapatite. This bond appeared very stable, as confirmed by the low dissolution rate of its calcium salt in water. The bonding potential of 4-methacryloxyethyl trimellitic acid (4-MET) was substantially lower. The monomer 2-methacryloxyethyl phenyl hydrogen phosphate (phenyl-P) and its bond to hydroxyapatite did not appear to be hydrolytically stable. Besides self-etching dentin, specific functional monomers have additional chemical bonding efficacy that is expected to contribute to their adhesive potential to tooth tissue.
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TL;DR: The present study demonstrated the evidence on synergistic spermatogenic effect of PHF as attributed in ayurveda for the treatment of oligospermia leading to infertility.
Abstract: The therapeutic use of natural herbs is an ancient human civilization act and the numbers of people have reliance on their pharmacological properties and preferred to use the natural herbs. People also use to consume these herbs as supplements to energize, bolster, and eventually enhance sexual ability. Polyherbal formulation (PHF) is one of these herbal amalgams that can be used to treat sexual dysfunction including erectile dysfunction, impotence, ejaculation dysfunction, and hypogonadism. The pilot study was aimed at evaluating the capacity of PHF in enhancing the spermatogenic potential of oligospermic patients. Thirty-six male patients with oligospermia were enrolled and randomized either to treatment (n = 23) with PHF (750 mg/d in three doses for 90 days) or to placebo (n = 13) in the same protocol. The preintervention semen analysis was compared with posttreatment semen analysis. Based on the postintervention semen analysis, patients were advised to undergo either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) to assess their fertility status. After polyherbal treatment, there was a 256% increase in sperm concentration (9.59 ± 4.37 × 106/mL to 25.61 ± 8.6 × 106/mL; P ≤0.001), 154% increase in semen volume (1.7 ± 0.14 mL to 4.32 ± 0.38 mL; P ≤0.001), and 215% increase in sperm motility (15.43 ± 2.40% to 48.65 ± 5.10%; P ≤ 0.001) on day 90 from baseline. Furthermore, a significant improvement and regulation were also observed in serum hormone levels with PHF treatment as compared to the placebo group. The present study demonstrated the evidence on synergistic spermatogenic effect of PHF as attributed in ayurveda for the treatment of oligospermia leading to infertility.
648 citations
TL;DR: Increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD, and further research is needed to elucidate the risks and mechanisms of soft tissues calcification with calcium supplementation in both healthy subjects and patients with chronic kidney disease.
Abstract: This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.
595 citations