Katja Diercke

Compression-dependent Up-regulation of Ephrin-A2 in PDL Fibroblasts Attenuates Osteogenesis

Members of the ephrin/Eph family have recently been shown to be involved in the regulation of bone homeostasis in a murine model. The activation of the EphB4 receptor on osteoblasts by its ligand ephrin-B2 led to stimulation of osteoblastogenesis and therefore to bone formation. The activation of ephrin-A2-EphA2 signaling on osteoblasts inhibited the activation of osteoblast-specific gene expression, leading to bone resorption. Fibroblasts within the periodontal ligament periodontal ligament may be one of the first responders to orthodontic forces. Periodontal ligament fibroblasts (PDLF) are mechanoresponsive. Members of the ephrin/Eph family might link mechanical forces received by PDLF with the regulation of osteoblastogenesis on osteoblasts of the alveolar bone. To study whether ephrin-A2 is modulated upon compression, we subjected human primary PDLF to static compressive forces (30.3 g/cm2). Static compressive forces significantly induced the expression of ephrin-A2, while the expression of ephrin-B2 was significantly down-regulated. Moreover, osteoblasts of the alveolar bone stimulated with ephrin-A2 in vitro significantly suppressed their osteoblastogenic gene expression (RUNX2, ALPL) and decreased signs of osteoblastic differentiation, as demonstrated by a significantly reduced ALP activity. Together, these findings establish a role for this ligand/receptor system linking mechanical forces with the regulation of osteogenesis during orthodontic tooth movement.

Strain-dependent Up-regulation of Ephrin-B2 Protein in Periodontal Ligament Fibroblasts Contributes to Osteogenesis during Tooth Movement

Background: Regulation of bone remodeling during orthodontic tooth movement. Results: Tensile stress induces ephrin-B2 expression in PDL fibroblasts, and ephrin-B2-EphB4 interactions induce osteoblastogenesis in osteoblasts of the alveolar bone. Conclusion: Ephrin-B2-EphB4 signaling between PDLF and osteoblasts of the alveolar bone might contribute to bone remodeling during orthodontic tooth movement. Significance: Understanding the regulation of bone remodeling during orthodontic tooth movement is a prerequisite for pharmacological interventions. During orthodontic tooth movement, the application of adequate orthodontic forces allows teeth to be moved through the alveolar bone. These forces are transmitted through the periodontal ligaments (PDL) to the supporting alveolar bone and lead to deposition or resorption of bone, depending on whether the tissues are exposed to a tensile or compressive mechanical strain. Fibroblasts within the PDL (PDLF) are considered to be mechanoresponsive. The transduction mechanisms from mechanical loading of the PDLF to the initiation of bone remodeling are not clearly understood. Recently, members of the ephrin/Eph family have been shown to be involved in the regulation of bone homeostasis. For the first time, we demonstrate that PDLF exposed to tensile strain induce the expression of ephrin-B2 via a FAK-, Ras-, ERK1/2-, and SP1-dependent pathway. Osteoblasts of the alveolar bone stimulated with ephrin-B2 increased their osteoblastogenic gene expression and showed functional signs of osteoblastic differentiation. In a physiological setting, ephrin-B2-EphB4 signaling between PDLF and osteoblasts of the alveolar bone might contribute to osteogenesis at tension sites during orthodontic tooth movement.

Dental fear in children and adolescents: a comparison of forms of anxiety management practised by general and paediatric dentists

BACKGROUND. About 11% of children and adolescents suffer from dental fear. These young people run an increasing risk of undergoing more invasive treatments. AIM. We researched the management of dental anxiety in young patients by general and paediatric dentists as well as by trained and untrained dentists. DESIGN. Eight hundred dentists in Germany were interviewed via e-mail regarding their experience, treatment techniques, information material and complications during the treatment of fearful children. We also examined how difficult dentists judge the treatment of anxious children and how often they participate in continuing education courses. RESULTS. Paediatric dentists applied a greater spectrum of management techniques than general dentists. They used more often psychotherapeutic interventions and anxiety assessment questionnaires. Dentists who frequently attend in continuing education courses judged the treatment to be less difficult and also used psychotherapeutic interventions more often. CONCLUSIONS. German paediatric dentists and dentists who take continuing education courses utilise a broader range of techniques to manage dental anxiety. They may be eminently suited to treat children with severe forms of anxiety. Therefore, dentists who treat young patients should participate in education programmes so as to reduce both the anxiety of their patients and their own anxiety.

Human primary cementoblasts respond to combined IL-1β stimulation and compression with an impaired BSP and CEMP-1 expression.

Cementoblasts are cells that produce, secrete and direct the production of cementum. Resorption lacunae occur in over 90% of teeth at the compression side of the periodontal ligament and might result in an irreversible loss of the original root length. We isolated and cultivated human primary cementoblasts and investigated their expression pattern concerning markers of the osteoblastogenic differentiation (RUNX2, OCN, ALP, and BSP) and CEMP-1. Compared to osteoblasts, cementoblasts displayed an expression pattern comparable to osteoblasts in an early stage of osteoblastogenic differentiation. Next, the human primary cementoblasts were stimulated with IL-1β (1 and 10ng/ml) for 24 and 96h and subsequently subjected to compressive forces (30.3g/cm(2)) for 1 and 6h. Our in vitro data demonstrated that BSP and CEMP-1 expression significantly decreased when stimulation was accompanied by compression, while compression or stimulation alone led to increased levels of BSP and decreased levels of CEMP-1. We concluded that human primary cementoblasts subjected to compression and IL-1β stimulation impeded BSP and CEMP-1 expression, proteins that are associated with cementogenesis.

Compression Induces Ephrin-A2 in PDL Fibroblasts via c-fos

Ephrin-A2–EphA2 and ephrin-B2–EphB4 interactions have been implicated in the regulation of bone remodeling. We previously demonstrated a potential role for members of the Eph-ephrin family of receptor tyrosine kinases for bone remodeling during orthodontic tooth movement: compression-dependent upregulation of ephrin-A2 in fibroblasts of the periodontal ligament (PDL) attenuated osteogenesis in osteoblasts of the alveolar bone. However, factors affecting the regulation of ephrin-A2 expression upon the application of compressive forces remained unclear. Here, we report a mechano-dependent pathway of ephrin-A2 induction in PDL fibroblasts (PDLFs) involving extracellular signal–regulated kinases (ERK) 1/2 and c-fos. PDLF subjected to compressive forces (30.3 g/cm2) upregulated c-fos and ephrin-A2 mRNA and protein expression and displayed increased ERK1/2 phosphorylation. Inhibition of the MAP kinase kinase (MEK)/ERK1/2 pathway using the specific MEK inhibitor U0126 significantly reduced ephrin-A2 messenger RNA upregulation upon compression. Silencing of c-fos using a small interfering RNA approach led to a significant inhibition of ephrin-A2 induction upon the application of compressive forces. Interestingly, ephrin-A2 stimulation of PDLF induced c-fos expression and led also to the induction of ephrin-A2 expression. Using a reporter gene construct in murine 3T3 cells, we found that ephrin-A2 was able to stimulate serum response element (SRE)–dependent luciferase activity. As the regulation of c-fos is SRE dependent, ephrin-A2 might induce c-fos via SRE activation. Taken together, we provide evidence for an ERK1/2- and c-fos–dependent regulation of ephrin-A2 in compressed PDLF and suggest a novel pathway for ephrin-A2 induction emanating from ephrin-A2 itself. We showed previously that ephrin-A2 at compression sites might contribute to tooth movement by inhibiting osteogenic differentiation. The regulatory pathway of ephrin-A2 induction during tooth movement identified in this study might be accessible for pharmacological interventions.

The management of dental anxiety and impact of psychosomatic factors on dentistry: Is recent scientific research translated into German dental practices?

This study investigated the dentists’ knowledge about psychosomatic medicine. Anxiolytic techniques, considerations about psychosomatic medicine, and referrals to psychotherapists were examined by a questionnaire. Overall, 65 percent felt negatively affected by patients with dental fear. Few dentists used relaxation techniques and hypnosis. The relationship between psychosomatic factors and pain perception was well known, but not their impact on wound healing. The frequency of continuing education courses correlated with a broader range of treatment techniques and less difficulties in treatment. Research evidence about the impact of psychological factors on dental treatment has not been translated into dental practice.

Biological evaluation of enamel sealants in an organotypic model of the human gingiva

OBJECTIVES Various sealant materials have been suggested to decrease decalcification during orthodontic treatment. However, only a few in vitro studies on the cytotoxicity of resinous pit and fissure sealants have been published, and to the best of our knowledge no similar studies are available for the enamel sealants used in orthodontics. Therefore, we aimed to characterize the possible adverse effects of enamel sealants, especially on the gingival epithelium. METHODS Organotypic cultures of the human gingival mucosa were used to assess the possible impact of six enamel sealants. Differentiation and apoptosis were determined by immunofluorescent staining. The pro-inflammatory cytokines IL-1β and IL-6 were quantified by ELISA. Cytotoxicity was measured using MTS assays in monolayer cultures of human gingival fibroblasts. Leaching of monomers from enamel sealants was quantified using HPLC. RESULTS The differentiation of the organotypic gingival mucosa remained unaffected. All under-cured and several standard-cured sealants (Light Bond™ Sealant, Light Bond™ Filled Sealant, and L.E.D. Pro Seal®) significantly induced apoptosis in the organotypic model. Light Bond™ Sealant, Light Bond™ Filled Sealant, and L.E.D. Pro Seal® caused a significant induction of pro-inflammatory cytokines. Reducing curing time had an influence on cytotoxicity in monolayer cultures of primary human oral cells. All resin-based sealants leached monomers. SIGNIFICANCE Enamel sealants might exert adverse effects on the gingival epithelium. Due to the vicinity of the enamel sealant to the gingival epithelium, and the large surface area of applied sealants, these materials should be carefully applied and sufficiently cured.

Prevalence of TMD symptoms in Turkish migrants and re-settlers from the former Soviet Union in comparison to a German group

Objectives: The objective of this study was to investigate the prevalence of temporomandibular disorder (TMD) symptoms among Turks and re-settlers with German origin from Russia and to compare those findings with a German group from the same area. Method: Sixty-nine Turkish migrants, 50 re-settlers, and 96 Germans were clinically examined according to a short version of the Research Diagnostic Criteria (RDC/TMD) protocol. The subjects participated in a feasibility study of the German National Cohort and were recruited from the study center Heidelberg/Mannheim of the cluster Baden-Württemberg/Saarland. Results: Significant differences emerged between the three ethnic groups for unassisted opening without pain, maximum unassisted opening, and overbite, with highest values for the German group. No significant differences were found for muscle pain on palpation or muscle and joint pain during opening. Discussion: As the authors identified significant differences between the different ethnic groups for metric measurements, it might be beneficial to include questions concerning the ethnicity to the German version of the RDC/TMD for further research, to make the results more comparable.