Association between facial measurements and polymorphisms in human epidermal growth factor and transforming growth factor β1

The aim of the study was to evaluate the association between genetic polymorphisms in human epidermal growth factor (EGF) (rs4444903) and transforming growth factor β1 – (TGF-β1) (rs1800470) with facial measurements in patients with dentofacial deformities. A total of 144 adult patients with dentofacial deformities were included. Facial linear and angular measurements were traced in lateral cephalometric radiographs used Dolphin 2D software. Cells from oral mucosa were collected for DNA to be extracted. The polymorphisms were genotyped using real-time polymerase chain reaction (PCR). Probabilites of less than 0.05 were accepted as significant. The rs4444903 heterozygous patients had a decrease in the mandibular length (p = 0.043) and the length of the mandibular base (p = 0.008), and homozygous A patients also had a reduction in the length of the mandibular base (p = 0.013) compared with homozygous G patients. Patients AG had an increase in measurement of the anterior facial height (p = 0.032) and in ANS-Me distance (p = 0.022) when compared with homozygous A. To the rs1800470, heterozygous patients had an increase in the length of the mandibular base (p = 0.043) when compared with homozygous A. Heterozygous AG patients had an increase in angular measurements in TGF-β1 polymorphism for the upper gonial angle, when compared with the homozygous AA (p = 0.032). Genetic polymorphisms in EGF and TGF-β1 are associated with facial measurements in a Brazilian population of patients with dentofacial deformities.     

Operculina turpethum extract inhibits growth and proliferation by inhibiting NF-κB,COX-2 and cyclin D1 and induces apoptosis by up regulating P53 in oral cancer cells

ObjectivesHerbal drugs are popularly emerging as complementary and alternative medicines in cancer patients because of their cost effectiveness and minimal side-effects. The extract of Operculina turpethum (OT) is known to have antipyretic, anti-inflammatory and purgative properties. Since it is popularly known have antiinflammatory activity, we investigated its anti-tumor activity on four oral squamous cell carcinoma cell lines (OSCC) namely, (SCC-4, KB, SCC-9 and SCC-25).DesignAntitumor activities of Operculina turpathum extract (OTE) was investigated by MTT and clonogenic assay, effect on cell cycle and apoptosis induction by Annexin-V/propidium iodide (PI) staining and flow cytometry and invasive potential of the tumor was determined by matrigel assay. The expression of various proteins involved in these mechanisms was analysed by western blotting.ResultsOTE specifically inhibited the growth and colony formation of OSCC cells in a dose-dependent manner via inhibiting NF-κB and its downstream target COX-2. It further arrested cell cycle at G0/G1 phase by inhibiting cyclin-D1 and induced early apoptosis by up-regulating P53 in OSCC cells. It also limits the invasion capacity of OSCC cells by up to 55–60%.ConclusionsOTE shows antitumor activities in OSCC cells by inhibiting NF-κB, COX-2 and cyclin D1 and upregulation of p53 expression. It may be developed as a safe and promising alternative chemopreventive/chemotherapeutic agent for oral cancer.     

Insulin-like growth factor 1 and transforming growth factor-β stimulate cystine/glutamate exchange activity in dental pulp cells

Introduction

The growth factors insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) are protective to dental pulp cells in culture against the toxicity of the composite materials Durafill VS and Flow Line (Henry Schein Inc, New York, NY). Because the toxicity of these materials is mediated by oxidative stress, it seemed possible that the protective effects of IGF-1 and TGF-β were through the enhancement of an endogenous antioxidant mechanism.

Methods

We used cultured dental pulp cells to determine the mechanism of the protective effects of IGF-1 and TGF-β, focusing on the glutathione system and the role of cystine/glutamate exchange (system xc-).

Results

We found that the toxicity of Durafill VS and Flow Line was attenuated by the addition of glutathione monoethylester, suggesting a specific role for the cellular antioxidant glutathione. Supporting this hypothesis, we found that IGF-1 and TGF-β were protective against the toxicity of the glutathione synthesis inhibitor buthionine sulfoximine. Because levels of cellular cystine are the limiting factor in the production of glutathione, we tested the effects of IGF-1 and TGF-β on cystine uptake. Both growth factors stimulated system xc-mediated cystine uptake. Furthermore, they attenuated the glutathione depletion induced by Durafill VS and Flow Line.

Conclusions

The results suggest that IGF-1 and TGF-β are protective through the stimulation of system xc-mediated cystine uptake, leading to maintenance of cellular glutathione. This novel action of growth factors on dental pulp cells has implications not only for preventing toxicity of dental materials but also for the general function of these cells.     

Are intrauterine growth restriction and preterm birth associated with dental caries?

OBJECTIVES: To assess the association between two intrauterine growth restriction (IUGR) surrogates - IUGR [small for gestational age birth (SGA) and fetal growth restriction (FGR)] and preterm birth with dental caries. METHODS: Data from the Third National Health and Nutritional Examination Survey (1988-1994) were used, including 2- to 5.9-year-old singletons (n = 3189). Dental caries was defined as presence of any teeth with dental caries (treated or untreated) and also as presence of at least two teeth with dental caries. Exposure variables were preterm birth (<37 gestational weeks), FGR, and SGA. Covariates included were poverty, race/ethnicity, age, sex, sucrose intake, environmental tobacco smoking, dental visits, education of head of household, breastfeeding, and use of baby bottle. Separate statistical analyses were conducted for IUGR and for preterm birth through the estimation of prevalence ratio (PR), taking complex sampling design into consideration and adjusting for confounders. Sensitivity analysis was conducted including and excluding 2-year-old children and also with the two definitions of dental caries. RESULTS: In general, the inclusion of 2-year-old children and the case definition of presence of any teeth with dental caries biased the results toward the null, but with no major changes in the results. In bivariate analysis, SGA and FGR birth were both negatively but not significantly associated with dental caries while a significant positive association was found for preterm birth. Sensitivity analysis showed that the PR for preterm in bivariate analysis varied from 1.65 (95% CI 1.14-2.40) to 1.84 (95% CI 1.19-2.83). After adjusting for confounders, the PR for preterm birth varied from 1.38 (95% CI 1.00-1.89) to 1.64 (95% CI 1.22-2.20). After adjustment, the PR for SGA varied from 0.79 (95% CI 0.56-101) to 0.66 (95% CI 0.33-0.96). For children from 3 to 5.9 years old, the adjusted PR for FGR using the category 'none' as reference were mild (PR 1.10; 95% CI 0.76-1.58), moderate (PR 0.66; 95% CI 0.26-167), and severe (PR 0.59; 95% CI 0.36-0.99). These values for FGR were very similar for the other models using other classifications of case definition or inclusion of 2-year-old children. CONCLUSIONS: Preterm birth was found to be positively associated with dental caries while there is an indication that SGA and FGR are negatively associated with dental caries. Although the negative association is counterintuitive, it is possible that increased antibiotic use and delayed tooth eruption may explain the negative association between IUGR and dental caries.     

Solubility of TTCP and β-TCP by solid titration

Objective

Using solid titration with hydroxyapatite (HAp) and octacalcium phosphate, HAp has been found to be more stable than dicalcium phosphate dihydrate (DCPD) even at lower pH, inconsistent with the widely reported view that DCPD is less soluble than other calcium phosphates below pH 4.2. A check of the behaviour of other calcium phosphates (TTCP; Ca/P: 2.00 and β-TCP; Ca/P: 1.33) is necessary.

Methods

Solid titration was used to determine the effective solubility of TTCP and β-TCP in 100 mM KCl solution at 37.0 ± 0.1 °C for pH ∼2.9-9.2 and ∼3-7.4 respectively. The constitution of the precipitate was determined by XRD, particle morphology was observed by SEM and TEM, and the precipitate Ca/P ratio was calculated by EDX.

Results

The only identified solid phase at equilibrium was HAp at both pH 3.60 and 4.50; no residual titrant or other phases were detected. A marked change of slope in the curve occurred at pH ∼3.9 for TTCP.

Conclusion

HAp was verified to be more stable than other calcium phosphates, especially at lower pH. That DCPD is more stable below pH 4.2 is contradicted.     

Smad7 blocks transforming growth factor-β1-induced gingival fibroblast-myofibroblast transition via inhibitory regulation of Smad2 and connective tissue growth factor

Background: Transforming growth factor‐β1 (TGF‐β1), its downstream signaling mediators (Smad proteins), and specific targets, including connective tissue growth factor (CTGF), play important roles in tissue remodeling and fibrosis via myofibroblast activation. We investigated the effect of overexpression of Smad7, a TGF‐β1 signaling inhibitor, on transition of gingival fibroblast to myofibroblast. Moreover, we analyzed the participation of CTGF on TGF‐β1–mediated myofibroblast transformation. Methods: To study the inhibitory effect of Smad7 on TGF‐β1/CTGF‐mediating gingival fibroblast transition into myofibroblasts, we stably overexpressed Smad7 in normal gingival fibroblasts and in myofibroblasts from hereditary gingival fibromatosis (HGF). Myofibroblasts were characterized by the expression of the specific marker isoform α of the smooth muscle actin (α‐SMA) by Western blot, flow cytometry, and immunofluorescence. Enzyme‐linked immunosorbent assay for type I collagen was performed to measure myofibroblast activity. CTGF's role on myofibroblast transformation was examined by enzyme‐linked immunosorbent assay and small interference RNA. Results: TGF‐β1 induced the expression of α‐SMA and CTGF, and small interference RNA–mediating CTGF silencing prevented fibroblast‐myofibroblast switch induced by TGF‐β1. In Smad7‐overexpressing fibroblasts, ablation of TGF‐β1–induced Smad2 phosphorylation marked decreased α‐SMA, CTGF, and type I collagen expression. Similarly, HGF transfectants overexpressing Smad7 demonstrated low levels of α‐SMA and phospho‐Smad2 and significant reduction on CTGF and type I collagen production. Conclusions: CTGF is critical for TGF‐β1–induced gingival fibroblast‐myofibroblast transition, and Smad7 overexpression is effective in the blockage of myofibroblast transformation and activation, suggesting that treatments targeting myofibroblasts by Smad7 overexpression may be clinically effective in gingival fibrotic diseases, such as HGF.     

Association between Björk's structural signs of mandibular growth rotation and skeletofacial morphology

The aim of this study was to apply Bj?rk's structural signs of mandibular growth rotation to answer the questions: (1) Is a hyperdivergent or hypodivergent skeletofacial growth pattern characterized by a specific mandibular morphology? (2) Are severe skeletofacial hyperor hypodivergencies recognized more easily than mild ones? (3) Are skeletofacial hyper- or hypodivergencies recognized more easily in older than in younger subjects? Mandibular cuttings from lateral head films of 135 Class I or Class II subjects were surveyed twice by nine observers. Of the 135 subjects, 95 subjects exhibited a large (ML/NSL > 38 degrees) and 40 a small (ML/NSL < 26 degrees) mandibular plane angle. Using the structural signs of mandibular growth rotation, the observers had to categorize the subjects as having either a high-angle or low-angle skeletofacial morphology. In 14% (13 of 95) of the subjects with a large ML/NSL angle, the skeletofacial hyperdivergency was recognized in all registrations, but in 19% (18 of 95), the hyperdivergency was identified in less than half of the registrations. In 63% (25 of 40) of the subjects with a small ML/NSL angle, the skeletofacial hypodivergency was recognized in all registrations, whereas in only 2.5% (one of 40), the hypodivergency was identified in less than half of the registrations. There was no association between the degree of hypo- or hyperdivergency or the age of the subjects and the number of correct registrations. Using the structural method of Bj?rk, it was difficult to categorize the subjects as having either a hyperor hypodivergent skeletofacial morphology. However, hypodivergency was recognized more easily than hyperdivergency.     

Dental compensation for moderate Class?III with vertical growth pattern by extraction of the lower second molars

Objectives

Analysis of the effects and side effects of treatment of patients with moderate skeletal Class?III and vertical growth pattern by means of extraction of the second molars in the lower jaw.

Patients and methods

A total of 20 patients with a mean age of 12.9 years were examined retrospectively. Inclusion criteria consisted of a Wits value of 0 to ?5, a posterior growth pattern of the mandible (Hasund analysis), an overjet of ?2 to 1?mm, and an overbite of 0 to ?3?mm. Treatment was performed using a straight-wire appliance. As part of the treatment, the lower second molars were extracted and Class?III elastics attached. Cephalograms and orthopantomograms taken before and after treatment were used for evaluation.

Results

Treatment resulted in a significant change in the mean overjet from 0.5?mm to 2.1?mm and the attainment of a positive mean overbite of ?1.0?mm to 0.9?mm. The occlusal plane rotated anteriorly from 18.8° to 13.7°. The skeletal parameters showed a change in the Wits value from ?3.3?mm to ?1.4?mm and an anterior mandibular rotation (ML-NSL 35.5° vs. 32.0°). The soft tissues revealed an increase in the distance between the lower lip and the ??esthetic line?? to the posterior (?2.0?mm vs. ?3.9?mm).

Conclusion

Dental compensation of moderate skeletal Class?III with a tendency to an anterior open bite with vertical growth pattern by extracting the lower second molars, combined with Class III elastics, resulted in an anterior rotation of the occlusal plane and mandible. Eighteen of 20 patients achieved a physiological overjet and positive overbite. A prerequisite for this therapy is the presence of lower wisdom teeth; a potential side effect is elongation of the upper second molars.     

Considerations of dentofacial growth in long-term retention and stability: is active retention needed?

It is extremely important to pay attention to the person's growth pattern, and a distinction must be made in the selection of retention devices on the basis of the nature and the extent of dentofacial dysplasia (growth pattern). The nature and duration of retention should depend on the maturation status of the patient and on anticipated future growth. Retention guidance is necessary for adjustment of the dentition to late growth changes and maturation of neuromuscular balance. "Active retention" is a concept we accept as readily as the orthopedic surgeon does for his scoliosis patients. There is some merit in the philosophy of those clinicians who advocate permanent retention guidance. Without always being aware of the biomechanics of growth change, they are in fact carrying the patient through the active stages of growth with their retention appliances. Finally, one may philosophize that nothing about the human morphology is stationary. Aging is a well-documented process of change. Lifetime dentitional adjustment and changing dental relationships are known to all, even in otherwise healthy persons. Then why do we expect long-term stability in every case? The answer to the question of long-term stability is long-term retention--dynamic, not static.     

Instructions for Authors by China Journal of Oral and Maxillofacial Surgery

China Journal of Oral and Maxillofacial Surgery (CJOMS)(ISSN 1672-3244), founded in November 8 2002, is an official journal of ChineseSociety of Oral and Maxillofacial Surgery, being designed to present the latest basic scientific and clinical findings of Oral and Maxillofacial Surgery inChina. It is published quarterly currently by Editorial Board of China Journal of Oral and Maxillofacial Surgery.     

Effect of cannabidiol on human gingival fibroblast extracellular matrix metabolism: MMP production and activity, and production of fibronectin and transforming growth factor β

Rawal SY, Dabbous MKh, Tipton DA. Effect of cannabidiol on human gingival fibroblast extracellular matrix metabolism: MMP production and activity, and production of fibronectin and transforming growth factor β. J Periodont Res 2012; 47: 320–329. © 2011 John Wiley & Sons A/S Background and Objective: Marijuana (Cannabis sativa) use may be associated with gingival enlargement, resembling that caused by phenytoin. Cannabidiol (CBD), a nonpsychotropic Cannabis derivative, is structurally similar to phenytoin. While there are many reports on effects of phenytoin on human gingival fibroblasts, there is no information on effects of Cannabis components on these cells. The objective of this study was to determine effects of CBD on human gingival fibroblast fibrogenic and matrix‐degrading activities. Material and Methods: Fibroblasts were incubated with CBD in serum‐free medium for 1–6 d. The effect of CBD on cell viability was determined by measuring activity of a mitochondrial enzyme. The fibrogenic molecule transforming growth factor β and the extracellular matrix molecule fibronectin were measured by ELISA. Pro‐MMP‐1 and total MMP‐2 were measured by ELISA. Activity of MMP‐2 was determined via a colorimetric assay in which a detection enzyme is activated by active MMP‐2. Data were analysed using ANOVA and Scheffe’s F procedure for post hoc comparisons. Results: Cannabidiol had little or no significant effect on cell viability. Low CBD concentrations increased transforming growth factor β production by as much as 40% (p < 0.001), while higher concentrations decreased it by as much as 40% (p < 0.0001). Cannabidiol increased fibronectin production by as much as approximately 100% (p < 0.001). Lower CBD concentrations increased MMP production, but the highest concentrations decreased production of both MMPs (p < 0.05) and decreased MMP‐2 activity (p < 0.02). Conclusion: The data suggest that the CBD may promote fibrotic gingival enlargement by increasing gingival fibroblast production of transforming growth factor β and fibronectin, while decreasing MMP production and activity.     

Synergistic induction of periodontal tissue regeneration by binary application of human osteogenic protein-1 and human transforming growth factor-β3 in Class II furcation defects of Papio ursinus

Teare JA, Petit J‐C, Ripamonti U. Synergistic induction of periodontal tissue regeneration by binary application of human osteogenic protein‐1 and human transforming growth factor‐β ₃ in Class II furcation defects of Papio ursinus. J Periodont Res 2012; 47: 336–344. © 2011 John Wiley & Sons A/S Background and Objective: Binary applications of recombinant human osteogenic protein‐1 (hOP‐1) and transforming growth factor‐β3 (hTGF‐β3) synergize to induce pronounced bone formation. To induce periodontal tissue regeneration, binary applications of hOP‐1 and hTGF‐β₃ were implanted in Class II furcation defects of the Chacma baboon, Papio ursinus. Material and Methods: Defects were created bilaterally in the furcation of the first and second mandibular molars of three adult baboons. Single applications of 25 μg hOP‐1 and 75 μg hTGF‐β₃ in Matrigel^® matrix were compared with 20:1 binary applications, i.e. 25 μg hOP‐1 and 1.25 μg hTGF‐β₃. Morcellated fragments of autogenous rectus abdominis striated muscle were added to binary applications. Sixty days after implantation, the animals were killed and the operated tissues harvested en bloc. Undecalcified sections were studied by light microscopy, and regenerated tissue was assessed by measuring volume and height of newly formed alveolar bone and cementum. Results: The hOP‐1 and hTGF‐β₃ induced periodontal tissue regeneration and cementogenesis. Qualitative morphological analysis of binary applications showed clear evidence for considerable periodontal tissue regeneration. Quantitatively, the differences in the histomorphometric values did not reach statistical significance for the group size chosen for this primate study. The addition of morcellated muscle fragments did not enhance tissue regeneration. Binary applications showed rapid expansion of the newly formed bone against the root surfaces following fibrovascular tissue induction in the centre of the treated defects. Conclusion: Binary applications of hOP‐1and hTGF‐β₃ in Matrigel^® matrix in Class II furcation defects of P. ursinus induced substantial periodontal tissue regeneration, which was tempered, however, by the anatomy of the furcation defect model, which does not allow for the rapid growth and expansion of the synergistic induction of bone formation, particularly when additionally treated with responding myoblastic stem cells.     

Instructions for Authors by China Journal of Oral and Maxillofacial Surgery

China Journal of Oral and Maxillofacial Surgery (CJOMS)(ISSN 1672-3244), founded in November 8 2002, is an official journal of Chinese Society of Oral and Maxillofacial Surgery, being designed to present the latest basic scientific and clinical findings of Oral and Maxillofacial Surgery in China. It is published quarterly currently by Editorial Board of China Journal of Oral and Maxillofacial Surgery.