Morphology of the sella turcica in Axenfeld–Rieger syndrome with PITX2 mutation

Background:  Axenfeld–Rieger syndrome (ARS) is a rare autosomal dominant disorder with an incidence of 1:200 000. Genotype and phenotype are heterogeneous and clinical morphology impresses with variable expressivity. Additionally to the typical craniofacial and dental aberrations anomalies in the morphology of sella turcica are discussed.
Method:  In a multidisciplinary genetic and clinical study four patients of a family with ARS were screened by direct DNA sequencing. Radiographic analysis of the patients was performed for evaluating cranial and dental structures. Additionally, a specific analysis of the morphology of the sella turcica was made on the radiographs.
Results:  Screening for PITX2 and FOXC1 mutations revealed a P64L missense mutation in PITX2 in all four patients. The cephalometric analysis showed a midface hypoplasia associated with a skeletal Class III. All patients showed a sella turcica bridge combined with a prominent posterior clinoid process followed by a steep clivus and an elongated sella turcica.
Conclusion:  The incidence of a sella turcica bridge in combination with a PITX2 mutation would suspect that sella turcica anomalies are typical symptoms of the syndrome. Sella turcica anomalies in association with craniofacial and dental aberrations, such as maxillary retrognathia, skeletal Class III relationship and hypoplasia of teeth, might be important indicators for ARS caused by PITX2 mutation.     

Craniofacial and dental features of Axenfeld-Rieger syndrome patients with PITX2 mutations

We aimed to characterize the genetic basis and craniofacial and dental features of Finnish patients with Axenfeld-Rieger syndrome (ARS). Mutational analyses of seven patients in five families were performed by sequencing or comparative genomic hybridization. Phenotypic analysis was based on both clinical and radiographic examinations, as well as on medical data. Lateral cephalometric radiographs of five patients were analysed using Viewbox 3.1-Cephalometric Software. The cephalometric values were compared to Finnish population-standard values of the same age and gender. Two frameshift mutations and three whole gene deletions were detected in five families. Class III skeletal relationship with retrognathic maxilla and mildly retrognathic mandible were detected in all five patients studied. Significant differences compared with the control values were in SNA (P = .0014), ANB (P = .0043) and SNB angles (P = .013). Five patients had anterior crossbite. Six patients showed tooth agenesis. The average number of missing teeth (third molars excluded) was 9 (range 0-15). The tooth agenesis rate was 52% in maxilla and 26% in mandible. Maxillary central and lateral permanent incisors were most often missing (rate 71% equally) while no one lacked canines or first molars in mandible. Two patients had a supernumerary mandibular permanent incisor. Six patients had either taurodontic and/or single-rooted molars. Our results suggest that class III skeletal relationship with maxillary and mandibular retrognathism, anterior crossbite, maxillary incisor agenesis and taurodontic, even pyramidal, roots are common determinants of ARS caused by PITX2 mutations.     

PITX2在牙齿早期发育中的作用

PITX2作为转录因子,在生物的早期发育中有很重要的作用.它与多个器官的发生发育都有着密切的联系,如心脏、血管、脑、肌肉、骨骼、眼睛等.而Pitx2对牙齿的影响则是通过Axenfeld-Rieger综合征发现的.本文就Pitx2与牙齿早期发育的某些相关基因之间相互作用进行综述.     

Novel identification of a four-base-pair deletion mutation in PITX2 in a Rieger syndrome family

Rieger syndrome is one of the most serious causes of tooth agenesis. Mutations in the PITX2, FOXC1, and PAX6 genes have been associated with Rieger syndrome. We have studied a three-generation Chinese family affected with Rieger syndrome and showing prominent dental abnormalities. Mutational screening and sequence analysis of the PITX2 gene revealed a previously unidentified four-base-pair deletion of nucleotides 717-720 in exon 5 in all affected members. The mutation causes a frame shift after Thr44, the 7th amino acid of the homeo-domain, and introduces a premature stop codon in the gene sequence. This deletion is the first unquestionable loss-of-function mutation, deleting all the functionally important parts of the protein. Our novel discovery indicates that the oligodontia and other phenotypes of Rieger syndrome observed in this family are due to this PITX2 mutation, and these data further support the critical role of PIXT2 in tooth morphogenesis.     

Evaluation of beta‐2 microglobulin and alpha‐2 macroglobulin levels in patients with different periodontal diseases

Background

Beta‐2 microglobulin (B2M) and alpha‐2 macroglobulin (A2M) play key roles in the immune system. The aim of this study was to compare B2M and A2M levels in patients with different periodontal diseases.

Methods

Eighty patients (20 periodontally healthy, 20 with gingivitis, 20 with chronic periodontitis and 20 with generalized aggressive periodontitis) were enrolled in the study. The analysis of B2M and A2M was performed on gingival crevicular fluid (GCF) using an enzyme‐linked immunosorbent assay in GCF.

Results

The total levels of B2M and A2M were statistically lower in the periodontally healthy group than in the other groups (p < 0.05) and significantly higher in the generalized aggressive periodontitis group compared to the other groups (p < 0.05).

Conclusions

B2M and A2M play key roles in the balance between periodontal health and disease. It is proposed that tissues release B2M and A2M to stop inflammation and inhibit the proliferation of microorganisms and this may be the reason for the high levels of B2M and A2M in the generalized aggressive periodontitis and chronic periodontitis groups. B2M and A2M are assumed to be user‐friendly and cost‐effective markers for periodontal disease to identify asymptomatic diseases.     

Molecular mimicry of Aggregatibacter actinomycetemcomitans with β2 glycoprotein I

Introduction: β2‐Glycoprotein I (β2GPI) is important in the suppression of coagulation, and antibodies against TLRVYK peptides on the β2GPI molecule are related to thrombosis. According to the Swiss‐Prot database, Aggregatibacter actinomycetemcomitans leukotoxin c has sequences (SIRVYK) that are homologous to the TLRVYK peptides. The aim of this study was to investigate the effects of A. actinomycetemcomitans infection on the antibody response against SIRVYK peptides in patients with periodontitis. Methods: Serum immunoglobulin G (IgG) antibody and IgG subclass antibody titers against SIRVYK or TLRVYK peptides were measured by enzyme‐linked immunosorbent assay in 46 patients with aggressive periodontitis (eight with localized disease, 38 with generalized disease), 28 patients with chronic periodontitis, and 20 periodontally healthy subjects. The presence of A. actinomycetemcomitans in plaque and saliva samples was determined using polymerase chain reaction. Results: The level of anti‐SIRVYK antibodies was significantly higher in patients who were A. actinomycetemcomitans‐positive than in A. actinomycetemcomitans‐negative patients (P < 0.05) in the chronic periodontitis group. A similar trend was found in the antibody response to TLRVYK peptide; however, no statistically significant difference was seen between A. actinomycetemcomitans‐positive and ‐negative patients. The A. actinomycetemcomitans‐positive patients displayed significantly higher levels of anti‐SIRVYK IgG2 and IgG3 antibodies than A. actinomycetemcomitans‐negative patients (P < 0.05 and P < 0.05, respectively). The level of IgG2 was highest among the four IgG subclasses and it predominantly increased in patients who were A. actinomycetemcomitans‐positive. Anti‐TLRVYK antibody levels were significantly correlated with anti‐SIRVYK IgG antibody levels. Conclusion: The results suggest that A. actinomycetemcomitans infection may elicit anti‐SIRVYK IgG antibodies and modify the anti‐TLRVYK antibody response in patients with periodontitis by molecular mimicry with β2GPI.     

The expressions of IGF‐1, BMP‐2 and TGF‐β1 in cartilage of condylar hyperplasia

Summary Condylar hyperplasia is a complex post‐natal growth abnormality of the mandible and condyle, which leads to facial asymmetry. We investigated the distributions of insulin‐like growth factors (IGF‐1), bone morphogenetic protein‐2 (BMP‐2) and transforming growth factor‐β1 (TGF‐β1) in cartilage of condylar hyperplasia and revealed relationships between age and the cartilaginous thickness. Twenty patients with condylar hyperplasia were divided into four histopathological types. The cartilaginous thickness and age in different histological types were analysed, and the localizations of IGF‐1, BMP‐2 and TGF‐β1 were detected by immunohistochemistry analysis. The cartilaginous thickness of condylar hyperplasia significantly increased. The cartilaginous thickness of type III was significantly thicker than type I and type II, Bivariate correlation revealed a significant correlations between age and the cartilaginous thickness (r = 0·68, P = 0·01). However, the expressions of IGF‐1, BMP‐2 and TGF‐β1 were the strongest in type I. In almost all types of condylar hyperplasia, the presence of IGF‐1 and BMP‐2 was found mainly in the proliferative chondrocyte layer and the hypertrophic chondrocyte layer, and only a few in the calcified chondrocyte layer. The presence of TGF‐β1 widely distributed from the fibrous articular surface to the calcified cartilage. These findings suggest that the proliferative activity of cartilage in condylar hyperplasia is strongly associated with age and cartilaginous thickness. Therefore, the four pathological types of condylar hyperplasia seem more likely to be four discontinuous stages.     

Human β‐defensin‐3 up‐regulates cyclooxygenase‐2 expression and prostaglandin E2 synthesis in human gingival fibroblasts

Chotjumlong P, Khongkhunthian S, Ongchai S, Reutrakul V, Krisanaprakornkit S. Human β‐defensin‐3 up‐regulates cyclooxygenase‐2 expression and prostaglandin E ₂ synthesis in human gingival fibroblasts. J Periodont Res 2010; 45: 464–470. © 2010 John Wiley & Sons A/S Background and Objective: Oral epithelial cells express three antimicrobial peptide human β‐defensins (hBDs) that have previously been demonstrated to exert proinflammatory effects on various immune cells. We wanted to examine whether hBDs could induce cyclooxygenase‐2 (COX‐2) expression and prostaglandin E₂ (PGE₂) synthesis in non‐immune cells, such as human gingival fibroblasts. Material and Methods: Cultured fibroblasts were treated with different concentrations of hBD‐1, ‐2, ‐3 or interleukin‐1β, as a positive control, for various times, in the presence or absence of NS‐398, a specific COX‐2 inhibitor. The levels of COX‐1 and COX‐2 mRNA expression were analyzed using RT‐PCR and real‐time PCR. Whole cell lysates were analyzed for COX‐1 and COX‐2 protein expression by western blotting. Cell‐free culture supernatants were assayed for PGE₂ levels by ELISA. The lactate dehydrogenase assay was performed to determine the cytotoxicity of hBDs. Results: Ten and 40 μg/mL of hBD‐3 up‐regulated COX‐2 mRNA and protein expression, consistent with COX‐2 up‐regulation by interleukin‐1β, whereas hBD‐1 and hBD‐2 did not. However, COX‐1 mRNA and protein were constitutively expressed. The time‐course study revealed that hBD‐3 up‐regulated COX‐2 mRNA and protein expression at 6 and 12 h, respectively. Consistent with COX‐2 up‐regulation, 10 and 40 μg/mL of hBD‐3 significantly increased PGE₂ levels in cell‐free culture supernatants (p < 0.05), and this was inhibited by NS‐398 in a dose‐dependent manner. Neither of the hBD concentrations tested in this study was toxic to the cells. Conclusion: These findings indicate that epithelial human β‐defensin‐3 functions as a proinflammatory mediator in controlling arachidonic acid metabolism in underlying fibroblasts.     

A Novel Regenerative Technique Combining Bone Morphogenetic Protein‐2 With Fibroblast Growth Factor‐2 for Circumferential Defects in Dog Incisors

Background: Periodontal regeneration of incisors is necessary for esthetic recovery. A novel regenerative method combining bone morphogenetic protein (BMP)‐2 and fibroblast growth factor (FGF)‐2 was developed. The purpose of this study is to evaluate periodontal healing, including root coverage, in circumferential defects of incisors. Methods: Fifty incisors in five beagles were used. After circumferential defects were surgically created, each group, consisting of ten recipient sites, received: 1) a double layer with FGF‐2 (2 μg)/collagen as inner layer and BMP‐2 (4 μg)/collagen as outer layer (FB‐DL group); 2) collagen impregnated with both FGF‐2 (2 μg) and BMP‐2 (4 μg) (FB‐M group); 3) BMP‐2 (4 μg)/collagen (B group); 4) FGF‐2 (4 μg)/collagen (F group); or 5) collagen (C group). Dogs were sacrificed 8 weeks post‐surgery, and healing was evaluated histologically. Results: The three groups treated with BMP‐2 showed enhanced new bone formation compared with control and F groups (P < 0.05). Furthermore, connective tissue attachment with cementum regeneration in the FB‐DL group was significantly greater than in FB‐M and B groups (P <0.05). Ankylosis in the FB‐DL group was significantly less than in FB‐M and B groups (P <0.05). Gingival recession was inhibited significantly better in FB‐DL and FB‐M groups compared with control and B groups. Conclusion: These data support development of a double‐layer method combining BMP‐2 and FGF‐2 as a therapeutic approach to periodontal regeneration at incisors with horizontal circumferential defects.     

整合素α2β1与药物性牙龈增生相关性的研究进展

药物性牙龈增生（DIGO）是指长期服用某些药物而引起的牙龈组织的纤维性增生和体积增大。牙龈细胞增多与胞外基质尤其是胶原蛋白的大量沉积是其主要病理表现。近年来研究表明,整合素α2β1与胶原吞噬作用密切相关,在DIGO的发生发展中发挥了重要作用。本文就整合素α2β1与DIGO相关性的研究进展进行综述。