Faculty Bibliography

Understanding the biology of tooth movement has great importance for developing techniques that increase the rate of tooth movement. Based on interpretations of data on the biology of tooth movement, the resulting accelerating techniques can be divided into two main groups: one group stimulates upstream events to indirectly activate downstream target cells, while the other group bypasses the upstream events and directly stimulates downstream target cells. In both approaches, there is a general consensus that the rate of tooth movement is controlled by the rate of bone resorption, which in turn is controlled by osteoclast activity. Therefore, to increase the rate of tooth movement, osteoclasts should be the target of treatment. In this article, both approaches will be reviewed and the biological limitations of each group will be discussed. (C) 2015 Elsevier Inc. All rights reserved.

Safe, minimally invasive, and cost-effective treatments are being sought to shortened orthodontic treatment time. Based on the well-known principle that orthodontic force triggers inflammatory pathways and osteoclast activity, we hypothesized that controlled micro-trauma in the form of micro-osteoperforations (MOPs) will amplify the expression of inflammatory markers that are normally expressed during orthodontic treatment and that this amplified response will accelerate both bone resorption and tooth movement. We tested our hypothesis in an animal model and in a human clinical trial. In adult rats, MOPs treatment significantly increased molar protraction with concomitant increase in inflammatory cytokine expression, osteoclastogenesis, and alveolar bone remodeling. Likewise, in human subjects, MOPs increased the rate of canine retraction concomitant with increased TNF alpha and IL-1 beta levels in gingival crevicular fluid. Moreover, MOPs treatment did not produce additional pain or discomfort in the patients tested. Our data supports our conclusion that MOPs offers a safe, minimally invasive, and easy mechanism to accelerate orthodontic tooth movement. (C) 2015 Elsevier Inc. All rights reserved.

Current systematic reviews are important for health care providers in supporting their evidence-based practice decisions. Equally important is the ability to determine when a new systematic review is needed in view of the rapid publication output. The current best evidence from a 2013 systematic review suggests that certain treatments may accelerate orthodontic tooth movement. Our aim was to determine if an updated systematic review is needed on this topic by applying the modified Ottawa method. A systematic search of Pubmed, Embase, CENTRAL, and Web of Science databases, identical to the previous systematic review, was executed. Two authors performed screening for inclusion/exclusion of studies and selected full-text articles were reviewed. Qualitative and quantitative criteria were applied to assess studies describing the following types of interventions to accelerate tooth movement: electrical, photobiomodulation, micro-osteoperforations, vibration, corticotomy, and low-level laser therapy. The Ottawa method showed that studies produced since 2011 have (1) potentially invalidating evidence and description of new methods and (2) combined new data that would enhance the precision of the existing evidence on low-level laser therapy. These collectively indicate the need for a new systematic review on adjunct procedures to accelerate orthodontic tooth movement, which may offer new evidence and techniques not previously mentioned. (C) 2015 Elsevier Inc. All rights reserved.

OBJECTIVES: Investigate the expression and activity of inflammatory markers in response to different magnitudes of orthodontic forces and correlate this response with other molecular and cellular events during orthodontic tooth movement. SETTING AND SAMPLE POPULATION: CTOR Laboratory; 245 Sprague Dawley male rats. METHODS AND MATERIALS: Control, sham, and 5 different experimental groups received different magnitudes of force on the right maxillary first molar using a coil spring. In the sham group, the spring was not activated. Control group did not receive any appliance. At days 1, 3, 7, 14, and 28, the maxillae were collected for RNA and protein analysis, immunohistochemistry, and micro-CT. RESULTS: There was a linear relation between the force and the level of cytokine expression at lower magnitudes of force. Higher magnitudes of force did not increase the expression of cytokines. Activity of CCL2, CCL5, IL-1, TNF-alpha, RANKL, and number of osteoclasts reached a saturation point in response to higher magnitudes of force, with unchanged rate of tooth movement. CONCLUSION: After a certain magnitude of force, there is a saturation in the biological response, and higher forces do not increase inflammatory markers, osteoclasts, nor the amount of tooth movement. Therefore, higher forces to accelerate the rate of tooth movement are not justified.

INTRODUCTION: Our objectives were to study the effect of micro-osteoperforations on the rate of tooth movement and the expression of inflammatory markers. METHODS: Twenty adults with Class II Division 1 malocclusion were divided into control and experimental groups. The control group did not receive micro-osteoperforations, and the experimental group received micro-osteoperforations on 1 side of the maxilla. Both maxillary canines were retracted, and movement was measured after 28 days. The activity of inflammatory markers was measured in gingival crevicular fluid using an antibody-based protein assay. Pain and discomfort were monitored with a numeric rating scale. RESULTS: Micro-osteoperforations significantly increased the rate of tooth movement by 2.3-fold; this was accompanied by a significant increase in the levels of inflammatory markers. The patients did not report significant pain or discomfort during or after the procedure, or any other complications. CONCLUSIONS: Micro-osteoperforation is an effective, comfortable, and safe procedure to accelerate tooth movement and significantly reduce the duration of orthodontic treatment.

This study aimed to determine the effect of a bioactive ceramic coating on titanium in the nanothickness range on human osteogenic cells, peripheral blood mononuclear cells (PBMC) and on osteogenic cells co-cultured with PBMC without exogenous stimuli. Cell viability, proliferation, adhesion, cytokine release (IL1beta, TGFbeta1, IL10 and IL17) and intracellular stain for osteopontin and alkaline phosphatase were assessed. Morphologic evaluation showed smaller and less spread cell aspects in co-culture relative to osteogenic cell culture. Cell viability, proliferation and adhesion kinetics were differently influenced by surface texture/chemistry in culture versus co-culture. Cytokine release was also influenced by the interaction between mononuclear and osteogenic cells (mediators released by mononuclear cells acted on osteogenic cells and vice versa). In general, 'multi-cell type' interactions played a more remarkable role than the surface roughness or chemistry utilized on the in vitro cellular events related to initial stages of bone formation.

The development of chondrogenic cell lines has led to major advances in the understanding of how chondrocyte differentiation is regulated, and has uncovered many signalling pathways and gene regulatory mechanisms required to maintain normal function. ATDC5 cells are a well established in vitro model of endochondral ossification; however, current methods are limited for mineralisation studies. In this study we demonstrate that culturing cells in the presence of ascorbic acid and 10 mM beta-glycerophosphate (betaGP) significantly increases the rate of extracellular matrix (ECM) synthesis and reduces the time required for mineral deposition to occur to 15 days of culture. Furthermore, the specific expression patterns of Col2a1 and Col10a1 are indicative of ATDC5 chondrogenic differentiation. Fourier transform-infrared spectroscopy analysis and transmission electron microscopy (TEM) showed that the mineral formed by ATDC5 cultures is similar to physiological hydroxyapatite. Additionally, we demonstrated that in cultures with betaGP, the presence of alkaline phosphatase (ALP) is required for this mineralisation to occur, further indicating that chondrogenic differentiation is required for ECM mineralisation. Together, these results demonstrate that when cultured in the presence of ascorbic acid and 10 mM betaGP, ATDC5 cells undergo chondrogenic differentiation and produce a physiological mineralised ECM from Day 15 of culture onwards. The rapid and novel method for ATDC5 culture described in this study is a major improvement compared with currently published methods and this will prove vital in the pursuit of underpinning the molecular mechanisms responsible for poor linear bone growth observed in a number of chronic diseases such as cystic fibrosis, chronic kidney disease, rheumatological conditions and inflammatory bowel disease.

Mechanical stimulation contributes to the health of alveolar bone, but no therapy using the osteogenic effects of these stimuli to increase alveolar bone formation has been developed. We propose that the application of high-frequency acceleration to teeth in the absence of significant loading is osteogenic. Sprague-Dawley rats were divided among control, sham, and experimental groups. The experimental group underwent localized accelerations at different frequencies for 5 min/day on the occlusal surface of the maxillary right first molar at a very low magnitude of loading (4 microepsilon). Sham rats received a similar load in the absence of acceleration or frequency. The alveolar bone of the maxilla was evaluated by microcomputed tomography (microCT), histology, fluorescence microscopy, scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR imaging), and RT-PCR for osteogenic genes. Results demonstrate that application of high-frequency acceleration significantly increased alveolar bone formation. These effects were not restricted to the area of application, and loading could be replaced by frequency and acceleration. These studies propose a simple mechanical therapy that may play a significant role in alveolar bone formation and maintenance.