GDF15 Modulates the Zoledronic-Acid-Induced Hyperinflammatory Mechanoresponse of Periodontal Ligament Fibroblasts.

Orthodontic tooth movement (OTM) is thought to be impeded by bisphosphonate (BP) therapy, mainly due to increased osteoclast apoptosis and changes in the periodontal ligament (PdL), a connecting tissue between the alveolar bone and teeth. PdL cells, mainly fibroblasts (PdLFs), are crucial regulators in OTM by modulating force-induced local inflammatory processes. Recently, we identified the TGF-ß/BMP superfamily member GDF15 as an important modulator in OTM, promoting the pro-inflammatory mechanoresponses of PdLFs. The precise impact of the highly potent BP zoledronate (ZOL) on the mechanofunctionality of PdLFs is still under-investigated. Therefore, the aim of this study was to further characterize the ZOL-induced changes in the initial inflammatory mechanoresponse of human PdLFs (hPdLFs) and to further clarify a potential interrelationship with GDF15 signaling. Thus, two-day in vitro treatment with 0.5 µM, 5 µM and 50 µM of ZOL altered the cellular properties of hPdLFs partially in a concentration-dependent manner. In particular, exposure to ZOL decreased their metabolic activity, the proliferation rate, detected using Ki-67 immunofluorescent staining, and survival, analyzed using trypan blue. An increasing occurrence of DNA strand breaks was observed using TUNEL and an activated DNA damage response was demonstrated using H2A.X (phosphoS139) staining. While the osteogenic differentiation of hPdLFs was unaffected by ZOL, increased cellular senescence was observed using enhanced p21Waf1/Cip1/Sdi1 and ß-galactosidase staining. In addition, cytokine-encoding genes such as IL6, IL8, COX2 and GDF15, which are associated with a senescence-associated secretory phenotype, were up-regulated by ZOL. Subsequently, this change in the hPdLF phenotype promoted a hyperinflammatory response to applied compressive forces with an increased expression of the pro-inflammatory markers IL1ß, IL6 and GDF15, as well as the activation of monocytic THP1 cells. GDF15 appeared to be particularly relevant to these changes, as siRNA-mediated down-regulation balanced these hyperinflammatory responses by reducing IL-1ß and IL-6 expression (IL1B p-value < 0.0001; IL6 p-value < 0.001) and secretion (IL-1ß p-value < 0.05; IL-6 p-value < 0.001), as well as immune cell activation (p-value < 0.0001). In addition, ZOL-related reduced RANKL/OPG values and inhibited osteoclast activation were enhanced in GDF15-deficient hPdLFs (both p-values < 0.0001; all statistical tests: one-way ANOVA, Tukey's post hoc test). Thus, GDF15 may become a promising new target in the personalized orthodontic treatment of bisphosphonatepatients.

Influence of the orthodontic bonding procedure on biofilm formation.

INTRODUCTION: In orthodontics, white spot lesions are a persistent and widespread problem caused by the demineralization of buccal tooth surfaces around bonded brackets. The remaining adhesive around the brackets leads to surface roughness, which might contribute to demineralization. The present in vitro study aimed to compare a conventional and a modern adhesive system (APC Flash-Free technology) for orthodontic brackets with regard to the adhesion of Streptococcus sobrinus, a leading caries pathogen. METHODS: This in vitro study included 20 premolar teeth and compared 10 APC Flash-Free adhesive-coated ceramic brackets (FF)with 10 conventionally bonded (CB) ceramic clarity brackets. Specimens were incubated in an S. sobrinus suspension for 3 h. To evaluate the bacterial formation, samples were analysed with a scanning electron microscope (SEM). Imaging software was used to quantify and statistically compare percentage values of colonization (PVC) in both groups' adhesion and transition areas. RESULTS: We found a significant difference in biofilm formation between the groups for the adhesive and transition areas. PVC in the adhesive area was approximately 10.3-fold greater for the CB group compared with the FF group (median: 3.2 vs 0.31; P < 0.0001). For the transition area, median PVC was approximately 2.4-fold greater for the CB group compared with the FF group (median: 53.17 vs 22.11; P < 0.01). CONCLUSIONS: There was a significantly lower level of S. sobrinus formation around the FF bracket system than there was surrounding the conventionally bonded group. This study suggests that the FF adhesive bracket system can help reduce the occurrence of bacterial growth around orthodontic brackets.

A Newly Developed Orthodontic-Logopedic Screening Procedure for Myofunctional Dysfunctions-A Pilot Study.

Interdisciplinary, patient-specific cooperation between orthodontics and speech therapy plays an important role in the therapy of myofunctional dysfunctions. The following orthodontic-logopedic screening procedure is intended to objectify the diagnosis of such dysfunctions and the progress of therapy. A diagnostic questionnaire was prepared based on existing diagnostic questionnaires for myofunctional dysfunction. It contains 32 questions, with a clinical weighting of 0 to 50 points in total. This results in a point score. The lower the score is, the lower the need for therapy is. The study included 108 patients between the ages of 6 and 50 years. After screening, the patient population was divided into Group 0 (score < 15; no speech therapy need; n = 36) and Group 1 (score ≥ 15; a speech therapy need; n = 72). Group 1 was additionally randomized into Subgroups A (with speech therapy; n = 36) and B (without speech therapy; n = 36). After a treatment interval of 6 months, all patients in Group 1 were examined again with the help of the screening procedure. Statistical analysis (SPSS) and significance testing (Mann-Whitney U test) were performed. At baseline, there was no significant difference between patients in Subgroups A and B (p = 0.157). Subgroup A had a median score of 25, and Subgroup B had a median score of 30. However, after the treatment interval, a significant improvement (p = 0.001) for Subgroup A with a median score of 11 (mean score difference = 14.67) over Subgroup B with a median score 23 (mean score difference of 7.08) was observed. The developed screening procedure was shown to be equally applicable to all patients and treatment providers. With the help of the scores in point form, the need for speech therapy and the progress of such therapy can be objectified.

Influence of Different Bracket Adhesive Systems on Enamel Demineralization-An In Vitro Study.

BACKGROUND: enamel demineralization is a common side effect of orthodontic therapy with fixed braces. The aim of the present in vitro study was to compare a conventional adhesive system and a modern adhesive system (APC Flash-Free [FF] technology) with regard to the demineralization of enamel by Streptococcus sobrinus (S. sobrinus). METHODS: this in vitro study included premolar teeth and compared APC FF adhesive brackets (Group A, n = 15) with conventional adhesive brackets (Group B, n = 15) from the same company. Specimens were incubated with a positive control group (PCG, n = 5) and a negative control group (NCG, n = 5) in an S. sobrinus suspension for three weeks. To evaluate the grade of enamel demineralization, the samples were analyzed using a polarizing microscope. RESULTS: the test specimens of group B with conventionally bonded bracket adhesive showed significantly greater (+10.8 µm) demineralization with regard to the penetration depth of the demineralization than the PCG (p = 0.012). Thus, there was a difference from group A with the new bracket adhesive of the FF brackets (+7.29 µm). Significantly, demineralization was more pronounced cervically than coronally in both groups, and it occurred cervically more frequently than grade 3 demineralization (p = 0.001). CONCLUSIONS: it seems plausible that new orthodontic bracket adhesives and the modern FF adhesive system positively contribute to the reduction in enamel demineralization during orthodontic treatment.

Influence of Root Post Materials and Aging on Fracture Strength and Marginal Gap Quality of Ceramic Crowns-An In Vitro Study.

The design of and materials for prosthodontic abutments and posts have significant influences on the fracture resistance of restored teeth. This in vitro study compared the fracture strength and marginal quality of full-ceramic crowns as a function of the inserted root posts via simulation of a five-year period of use. Test specimens were prepared from 60 extracted maxillary incisors using titanium L9 (A), glass-fiber L9 (B), and glass-fiber L6 (C) root posts. The circular marginal gap behavior, linear loading capacity, and material fatigue after artificial aging were investigated. The marginal gap behavior and material fatigue were analyzed using electron microscopy. The linear loading capacity of the specimens was investigated using the Zwick Z005 universal testing machine. None of the tested root post materials showed statistically significant differences in marginal width values (p = 0.921), except in the case of marginal gap location. For Group A, there was a statistically significant difference from the labial to the distal (p = 0.012), mesial (p = 0.000), and palatinal (p = 0.005). Similarly, Group B showed a statistically significant difference from the labial to the distal (p = 0.003), mesial (p = 0.000), and palatinal (p = 0.003). Group C showed a statistically significant difference from the labial to the distal (p = 0.001) and mesial (p = 0.009). Linear load capacity reached mean values of 455.8-537.7 N, and micro-cracks occurred after artificial aging, predominantly in Groups B and C. Through the chosen experimental design, it was shown that the root post material and root post length had no influence on the fracture strength of the test teeth before or after artificial aging. However, the marginal gap location depends on the root post material and its length, which is wider mesially and distally and also tends to be greater palatinally than labially.

Effects of reducing excess dental adhesive on bacterial adhesion in the bracket periphery.

OBJECTIVES: White spot lesions are one of the most common side effects of orthodontic therapy with a multibracket appliance and may indicate a preliminary stage of caries, also known as initial caries. Several approaches may be utilized to prevent these lesions, such as reducing bacterial adhesion in the area surrounding the bracket. This bacterial colonization can be adversely affected by a number of local characteristics. In this context, the effects of excess dental adhesive in the bracket periphery were investigated by comparing a conventional bracket system with the APC flash-free bracket system. MATERIALS AND METHODS: Both bracket systems were applied to 24 extracted human premolars, and bacterial adhesion with Streptoccocus sobrinus (S. sobrinus) was performed for 24 h, 48 h, 7 d, and 14 d. After incubation, bacterial colonization was examined in specific areas by electron microscopy. RESULTS: Overall, significantly fewer bacterial colonies were found in the adhesive area around the APC flash-free brackets (n = 507 ± 13 bacteria) than the conventionally bonded bracket systems (n = 850 ± 56 bacteria). This is a significant difference (**p = 0.004). However, APC flash-free brackets tend to create marginal gaps with more bacterial adhesion in this area than conventional bracket systems (n = 265 ± 31 bacteria). This bacterial accumulation in the marginal-gap area is also significant (*p = 0.029). CONCLUSION: A smooth adhesive surface with minimal adhesive excess is beneficial for reducing bacterial adhesion but also poses a risk of marginal gap formation with subsequent bacterial colonization, which can potentially trigger carious lesions. CLINICAL RELEVANCE: To reduce bacterial adhesion, the APC flash-free bracket adhesive system with low adhesive excess might be beneficial. APC flash-free brackets reduce the bacterial colonization in the bracket environment. A lower number of bacteria can minimize white spot lesions in the bracket environment. APC flash-free brackets tend to form marginal gaps between the bracket adhesive and the tooth.