Mechanobiology of orthodontic tooth movement: An update.

The purpose of this review is to provide an update on the changes at the cellular and tissue level occurring during orthodontic force application. For the understanding of this process, knowledge of the mechanobiology of the periodontal ligament and the alveolar bone are essential. The periodontal ligament and alveolar bone make up a functional unit that undergoes robust changes during orthodontic tooth movement. Complex molecular signaling is responsible for converting mechanical stresses into biochemical events with a net result of bone apposition and/or bone resorption. Despite an improved understanding of mechanical and biochemical signaling mechanisms, it is largely unknown how mechanical stresses regulate the differentiation of stem/progenitor cells into osteoblast and osteoclast lineages. To advance orthodontics, it is crucial to gain a better understanding of osteoblast differentiation from mesenchymal stem/progenitor cells and osteoclastogenesis from the hematopoietic/monocyte lineage.

Age effect on orthodontic tooth movement rate and the composition of gingival crevicular fluid : A literature review.

PURPOSE: To evaluate and form a comprehensive understanding of the effect of patient age on bone remodeling and consequently on the rate of orthodontic tooth movement (OTM). METHODS: A systematic search in PubMed and Embase from 1990 to December 2017 was performed and completed by a hand search. Prospective clinical trials which investigated the rate of OTM and/or studies assessing age-related changes in the composition of gingival crevicular fluid (GCF) in older compared to younger study groups were included. Study selection, data extraction and risk of bias were assessed by two authors. RESULTS: Eight studies fulfilled the inclusion criteria. Among them, four evaluated the rate of OTM and six investigated mediators in the GCF (prostaglandin E2, interleukin [IL]-1ß, IL­6, IL­1 receptor antagonist, receptor activator of nuclear factor kappa­Β ligand, osteoprotegerin, granulocyte-macrophage colony-stimulating factor, pentraxin 3). Patient age ranged between 16 and 43 years for older and <16 years for younger groups. In most of the studies, the younger patients showed faster OTM in the first phase of treatment and more pronounced cytokine levels. Older patients had a delayed reaction to orthodontic forces. CONCLUSION: The small number of included studies and large heterogeneity in study design give limited clinical evidence that the older patients are less responsive to orthodontic force in comparison to younger patients. The initial cellular response to orthodontic force is expected to be delayed in older patients. Control intervals during orthodontic treatment should be adjusted to the individual's treatment response.

Update on 13 Syndromes Affecting Craniofacial and Dental Structures.

Care of individuals with syndromes affecting craniofacial and dental structures are mostly treated by an interdisciplinary team from early childhood on. In addition to medical and dental specialists that have a vivid interest in these syndromes and for whom these syndromes are of evident interest, experts of scientific background-like molecular and developmental geneticists, but also computational biologists and bioinformaticians-, become more frequently involved in the refined diagnostic and etiological processes of these patients. Early diagnosis is often crucial for the effective treatment of functional and developmental aspects. However, not all syndromes can be clinically identified early, especially in cases of absence of known family history. Moreover, the treatment of these patients is often complicated because of insufficient medical knowledge, and because of the dental and craniofacial developmental variations. The role of the team is crucial for the prevention, proper function, and craniofacial development which is often combined with orthognathic surgery. Although the existing literature does not provide considerable insight into this topic, this descriptive review aims to provide tools for the interdisciplinary team by giving an update on the genetics and general features, and the oral and craniofacial manifestations for early diagnosis. Clinical phenotyping together with genetic data and pathway information will ultimately pave the way for preventive strategies and therapeutic options in the future. This will improve the prognosis for better functional and aesthetic outcome for these patients and lead to a better quality of life, not only for the patients themselves but also for their families. The aim of this review is to promote interdisciplinary interaction and mutual understanding among all specialists involved in the diagnosis and therapeutic guidance of patients with these syndromal conditions in order to provide optimal personalized care in an integrated approach.

Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats.

Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, "fast" and "slow" tooth movers during orthodontic treatment.

Age-related changes of dental pulp tissue after experimental tooth movement in rats.

It is generally accepted that the effect of orthodontic tooth movement on the dental pulp in adolescents is reversible and that it has no long-lasting effect on pulpal physiology. However, it is not clear yet if the same conclusion is also valid for adult subjects. Thus, in two groups of rats, aged 6 and 40 weeks respectively, 3 molars at one side of the maxilla were moved together in a mesial direction with a standardized orthodontic appliance delivering a force of 10 cN. The contralateral side served as a control. Parasagittal histological sections were prepared after tooth movement for 1, 2, 4, 8, and 12 weeks. The pulp tissue was characterized for the different groups, with special emphasis on cell density, inflammatory cells, vascularity, and odontoblasts. Dimensions of dentin and the pulpal horns was determined and related with the duration of orthodontic force application and age ware evaluated. We found that neither in young nor in adult rats, force application led to long-lasting or irreversible changes in pulpal tissues. Dimensional variables showed significant age-related changes. In conclusion, orthodontic tooth movement per se has no long-lasting or irreversible effect on pulpal tissues, neither in the young nor in the adult animals.

Delayed cutaneous wound closure in HO-2 deficient mice despite normal HO-1 expression.

Impaired wound healing can lead to scarring, and aesthetical and functional problems. The cytoprotective haem oxygenase (HO) enzymes degrade haem into iron, biliverdin and carbon monoxide. HO-1 deficient mice suffer from chronic inflammatory stress and delayed cutaneous wound healing, while corneal wound healing in HO-2 deficient mice is impaired with exorbitant inflammation and absence of HO-1 expression. This study addresses the role of HO-2 in cutaneous excisional wound healing using HO-2 knockout (KO) mice. Here, we show that HO-2 deficiency also delays cutaneous wound closure compared to WT controls. In addition, we detected reduced collagen deposition and vessel density in the wounds of HO-2 KO mice compared to WT controls. Surprisingly, wound closure in HO-2 KO mice was accompanied by an inflammatory response comparable to WT mice. HO-1 induction in HO-2 deficient skin was also similar to WT controls and may explain this protection against exaggerated cutaneous inflammation but not the delayed wound closure. Proliferation and myofibroblast differentiation were similar in both two genotypes. Next, we screened for candidate genes to explain the observed delayed wound closure, and detected delayed gene and protein expression profiles of the chemokine (C-X-C) ligand-11 (CXCL-11) in wounds of HO-2 KO mice. Abnormal regulation of CXCL-11 has been linked to delayed wound healing and disturbed angiogenesis. However, whether aberrant CXCL-11 expression in HO-2 KO mice is caused by or is causing delayed wound healing needs to be further investigated.

The oxytalan fibre network in the periodontium and its possible mechanical function.

The biomechanical character of the periodontal ligament (PDL) is crucial in its response to functional and orthodontic forces. Collagen has been the primary subject of investigations in this field. Several studies, however, indicate that oxytalan fibres, which belong to the elastic fibre family, also contribute to the biomechanical character and behaviour of the PDL. In order to elucidate this, we have evaluated the available literature on the oxytalan fibre network within the PDL and supra-alveolar tissues with respect to development, morphology and distribution, and response to mechanical stimulation. To this end, we have combined the classical histological studies with more recent in vitro studies. Oxytalan fibres develop simultaneously with the root and the vascular system within the PDL. A close association between oxytalan fibres and the vascular system also remains later in life, suggesting a role in vascular support. Mechanical loading of the PDL, through orthodontic force application, appears to induce an increase in the number, size, and length of oxytalan fibres. In line with this, in vitro stretching of PDL fibroblasts (PDLFs) results in an increased production of fibrillin, a major structural component of the microfibrils that make up oxytalan fibres. The available data suggest a mechanical function for oxytalan, but to date experimental data are limited. Further research is required to clarify their exact mechanical function and possible role in orthodontic tooth movement.

Inflammatory responses in two commonly used rat models for experimental tooth movement: comparison with ligature-induced periodontitis.

OBJECTIVE: To compare two often used rat models for experimental tooth movement, namely the elastic band, and the coil spring model. They were compared with a silk-ligature-induced periodontitis model. DESIGN: Thirty six, 6-weeks-old rats were used. In a split mouth design four experimental conditions were allocated by permutation: (1) insertion of an orthodontic elastic band between the maxillary first and the second molar, (2) placement of a silk ligature around the cervix of the upper second molar, (3) a 10cN NiTi coil spring for mesial movement of the three maxillary molars as one block, and (4) Control. After 1, 3, and 5 days, rats were killed and immunohistochemical staining for ED1, cathepsin K, and MMP9 was performed. RESULTS: A time-dependent increase in the inflammatory infiltration of the interdental papilla was found in the elastic band and the ligature model, but not in the spring model. The disruption of the epithelium of the interdental papilla and the transseptal fibers was less severe in the spring group than in the other two experimental groups. All three experimental groups showed a time-dependent resorption of the interdental bony septum. However, this started faster and was more severe in the elastic band and the ligature than in the spring group. The numbers of cathepsin K+ and MMP9+ cells were higher in the elastic band and the ligature group than in the spring group. CONCLUSIONS: Elastic bands yield similar periodontal effects as ligatures. The spring model is to be preferred for experimental tooth movement studies.

Dentoalveolar development in beagle dogs after palatal repair with a dermal substitute.

INTRODUCTION: Our aim was to compare the dentoalveolar development in beagle dogs after palatal repair according to the Von Langenbeck technique with and without implantation of a dermal substitute. METHODS: Nineteen beagles (age, 12 weeks) were assigned to 2 experimental groups and an untreated control group. Palatal surgery was performed with the Von Langenbeck technique in the 2 experimental groups. The dermal substitute Integra (Plainsboro, NJ, USA) was implanted in 1 experimental group, and the other served as sham group. Dental casts were made before surgery and at several times in all groups to measure dentoalveolar development. Transversal distances, arch depth, tipping, and rotation were determined. Histologic evaluations were performed at 3, 7, and 15 weeks after surgery. The degrees of reepithelialization and tissue organization were evaluated microscopically. RESULTS: All wounds healed without complications. Scar tissue attached to the bone was found in both experimental groups. Deposition of bone in the Integra occurred after implantation, indicating its osteoconductivity. Transversal dentoalveolar development was similar in both experimental groups, but it was significantly less than in the control group. CONCLUSIONS: Implantation of Integra after the Von Langenbeck procedure for palatal repair does not improve dentoalveolar development.

Osteoclast differentiation and recruitment during early stages of experimental tooth movement in rats.

Osteoclasts are derived from macrophage-lineage precursors. ED1 is an antibody that can recognize this lineage of cells. Matrix metalloproteinase 9 (MMP9) is essential for the migration of osteoclasts and their precursors during osteoclastogenesis. The aim of this research was to investigate differentiation and recruitment of osteoclasts during the early phase of experimental tooth movement in rats. The upper three molars of Wistar rats at one side were moved mesially, using Ni-Ti coil springs of 10 cN, for 6, 12, 24, 36, 48, 72, 96, and 120 h. The contralateral sides served as controls. Immunohistochemical staining using ED1 and MMP9 antibodies was performed. ED1(+) and MMP9(+) mononuclear and multinuclear cells were counted and statistically analysed. After force application, the number of ED1(+)/MMP9(+) multinuclear cells first increased in the bone marrow. At compressed areas, the number of ED1(+) mononuclear cells decreased; this was followed by an increase in the number of ED1(+/)MMP9(+) mononuclear and multinuclear cells. At tension areas, the number of ED1(+)/MMP9(+) multinuclear cells decreased while the number of ED1(+) mononuclear cells remained stable. It was concluded that force application induces osteoclast differentiation within the bone marrow. These osteoclasts probably migrate subsequently into the compressed PDL. Pre-existing osteoclasts disappear at the tension areas while the number of mononuclear macrophage-lineage cells remains stable.

Medication effects on the rate of orthodontic tooth movement: a systematic literature review.

INTRODUCTION: Recently, several reviews have been published on the effects of medications on bone physiology and the clinical side effects in orthodontics. However, the effects of medications on the rate of orthodontic tooth movement have not been evaluated. METHODS: A systematic literature review on the effects of medications and dietary supplements on the rate of experimental tooth movement was performed by using PubMed (1953-Oct 2007), Web of Science, and Biosis, complemented by a hand search. RESULTS: Forty-nine articles were included in the review, but their interpretation was hindered by the variability in experimental design, magnitude of force applied during tooth movement, and medication regimens. Therapeutic administration of eicosanoids resulted in increased tooth movement, whereas their blocking led to a decrease. Nonsteroidal anti-inflammatory drugs (NSAIDs) decreased tooth movement, but non-NSAID analgesics, such as paracetamol (acetaminophen), had no effect. Corticosteroid hormones, parathyroid hormone, and thyroxin have all been shown to increase tooth movement. Estrogens probably reduce tooth movement, although no direct evidence is available. Vitamin D3 stimulates tooth movement, and dietary calcium seemed to reduce it. Bisphosphonates had a strong inhibitory effect. CONCLUSIONS: Medications might have an important influence on the rate of tooth movement, and information on their consumption is essential to adequately discuss treatment planning with patients.

Age-related changes of periodontal ligament surface areas during force application.

OBJECTIVE: To investigate the age-dependent morphology of the periodontal ligament (PDL) tissue and changes in its surface area (SA) during force application provided with a standardized orthodontic setup for a period of 12 weeks in young and adult rats. METHODS: Two groups of 30 rats, age 6 weeks and 9 to 12 months, were used. Orthodontic appliances were placed to move the maxillary molars mesially with the contralateral sides used as controls. At 1, 2, 4, 8, and 12 weeks, groups of animals were killed. The PDL SA and the PDL SA ratio between pressure and tension regions were determined. RESULTS: An age-related decrease in the PDL SA was noted at control sides. Significant changes during the experimental period occurred only at experimental sides: The PDL SA was smaller at pressure than at tension regions only at week 1 in young rats; in adult rats, the difference between the two regions was significant at week 8. These changes were confirmed by the morphologic disorganization of the PDL and alterations in the PDL SA ratio. CONCLUSIONS: During force application, the PDL at the pressure regions became disorganized and subsequently was reorganized, as is shown by the histologic changes and SA of the PDL over time. This process occurred earlier and was more prominent in young rats; it occurred later and was more prolonged in adult animals.

Putative golden proportions as predictors of facial esthetics in adolescents.

INTRODUCTION: In orthodontics, facial esthetics is assumed to be related to golden proportions apparent in the ideal human face. The aim of the study was to analyze the putative relationship between facial esthetics and golden proportions in white adolescents. METHODS: Seventy-six adult laypeople evaluated sets of photographs of 64 adolescents on a visual analog scale (VAS) from 0 to 100. The facial esthetic value of each subject was calculated as a mean VAS score. Three observers recorded the position of 13 facial landmarks included in 19 putative golden proportions, based on the golden proportions as defined by Ricketts. The proportions and each proportion's deviation from the golden target (1.618) were calculated. This deviation was then related to the VAS scores. RESULTS: Only 4 of the 19 proportions had a significant negative correlation with the VAS scores, indicating that beautiful faces showed less deviation from the golden standard than less beautiful faces. Together, these variables explained only 16% of the variance. CONCLUSIONS: Few golden proportions have a significant relationship with facial esthetics in adolescents. The explained variance of these variables is too small to be of clinical importance.

Osteoclast differentiation during experimental tooth movement by a short-term force application: an immunohistochemical study in rats.

OBJECTIVE: The origin of osteoclasts responsible for bone resorption during orthodontic tooth movement is not yet clear. Their precursors may reside within the periodontal ligament (PDL) or could be recruited from the circulation or the bone marrow. The aim of this study was to investigate the spatial and sequential distribution of osteoclast precursors during experimental tooth movement by using three differentiation markers: receptor for macrophage colony stimulating factor (c-Fms), receptor activator of nuclear factor-kappaB (RANK), and calcitonin receptor (CTR). MATERIAL AND METHODS: Six-week-old Wistar rats were used. Elastic bands were inserted between the upper 1st and 2nd molars for 1, 2, 3, and 6 days. Immunohistochemical staining for c-Fms, RANK, or CTR was performed on parasagittal sections and positive cells were counted. RESULTS: Before force application, many c-Fms+ and a few RANK+ precursors were present in the bone marrow. No c-Fms+ osteoclast precursors were observed in the PDL. After force application, the number of RANK+ but not c-Fms+ precursors increased rapidly in the PDL. In bone marrow, the number of c-Fms+ and RANK+ precursors also increased rapidly, as did multinuclear c-Fms+, RANK+, and CTR+ cells. Subsequently, the number of c-Fms+, RANK+, and CTR+ multinuclear cells in the PDL increased. After 6 days, the expression profiles tended to return to baseline levels. CONCLUSION: Osteoclast precursors differentiate within the bone marrow and then migrate into the PDL during early tooth movement.

Effect of duration of force application on blood vessels in young and adult rats.

INTRODUCTION: Age effects on orthodontically induced periodontal vascular reactions have not been studied. The aim of the present study was to test the hypothesis that prolonged tooth movement induces age-related increases in periodontal vascularity. METHODS: A standardized orthodontic appliance was placed in 2 groups of 30 rats aged 6 weeks and 9 to 12 months. At 1, 2, 4, 8, and 12 weeks, animals were killed. Blood vessels (BV) were identified based on their morphology and by immunohistochemical staining for alpha-smooth muscle actin. At each study region, surface areas (SA) of the periodontal ligament space and each BV were measured; BV mean SA, BV relative SA (the summed BV SA as a percentage of the periodontal ligament SA), and BV numbers were calculated. RESULTS: Pressure and tension regions showed similar vascular changes. Young rats had lower BV relative SA and BV mean SA in the early phase of force application (< 4 weeks); this increased in the late phase, reaching the same level as adult rats. In the late phase (4-12 weeks), young rats had increases of both small- and large-sized BV that did not affect the BV mean SA; adult rats had an increase of small-sized BV only; this resulted in decreased BV mean SA. CONCLUSIONS: The hypothesis was confirmed that prolonged tooth movement increases periodontal vascularity, which is age related. These results suggest that clinicians should consider age-related difference in tissue reactions during orthodontic tooth movement.

Age-dependent external root resorption during tooth movement in rats.

OBJECTIVE: To investigate the effect of age on root resorption and distribution along different parts of the root during prolonged light force application. MATERIAL AND METHODS: Orthodontic appliances were placed in two groups of 30 rats (one group 6 weeks old, the other 9-12 months old), with contralateral sides as controls. Groups of animals were killed at 1, 2, 4, 8, and 12 weeks. At the study site, incidence was counted as either 1 (with resorption) or 0 (without); severity was measured as the summed length of all resorption lacunae as a percentage of study total root length. RESULTS: Young and adult rats had the same incidence of root resorption in the early phase (<4 weeks), and both increased in the late phase (4-12 weeks) to the same level. Severity of resorption increased with prolonged tooth movement only in adult rats. However, there was no age-related difference in either the early or the late phase. In both groups, the middle part of the root had the highest incidence of resorption; the most severe resorption occurred exclusively at this part. CONCLUSION: Orthodontic intervention even with light forces increased both the incidence and severity of root resorption, the more so in the middle part of the root. Adult rats had increased incidence and severity with prolonged tooth movement.

Panel perception of change in facial aesthetics following orthodontic treatment in adolescents.

The aim of the study was to evaluate the influence of the characteristics of panel members, the effects of gender and Angle Class of adolescent patients on their change in facial aesthetics following orthodontic treatment, and to assess the optimal panel size for epidemiological studies on changes in facial aesthetics after orthodontic treatment. A panel of 74 adult laymen (35 males and 39 females) and a panel of 87 orthodontists (37 males and 50 females) evaluated sets of three post-treatment standardized photographs (one frontal, one three-quarter smiling, and one lateral) of 64 adolescent orthodontic patients in relation to the pre-treatment sets of the same patient on a five-point scale. The main effects of professional background, age, gender, and geographic region of the panel members on the aesthetic scores, as well as their first order interactions were evaluated by multilevel models. Professional background, age, gender, and geographical region of panel members have an influence on the evaluation of the change of facial aesthetics following orthodontic treatment. The effect of gender and Angle Class of the patients on the scores was evaluated by two-way analysis of variance. There was no difference in the mean scores for boys and girls. Improvement of facial aesthetics by orthodontic treatment was significant for Class I, Class II division 1, and Class II division 2 patients, but not for Class III patients. Based on the intraclass correlation coefficient, a panel of nine randomly selected orthodontists, a panel of 14 randomly selected laymen, or a mixed panel of 13 individuals is sufficient to obtain reliable results in the aesthetic evaluation of adolescent faces, using photographs and a five-point scale.

Facial esthetics in adolescents and its relationship to "ideal" ratios and angles.

INTRODUCTION: Many guidelines, norms, and ideal ratios and angles for attractive faces have been proposed in the literature. The aim of this study was to test the hypothesis that facial attractiveness in adolescents is related to ideal angles and ratios, as indicated in the literature. METHODS: Seventy-six laypeople viewed sets of photographs of 64 adolescents and rated them on a visual analog scale (VAS) from 0 to 100. The facial esthetic value of each subject was calculated as a mean VAS score. Three observers recorded the positions of 61 landmarks, and 45 were found to have acceptable reproducibility. Based on these 45 landmarks, 27 ideal ratios on frontal photographs and 26 ideal angles on lateral photographs were identified in the literature. These ratios and angles were calculated on each photograph, and their deviation from the ideal targets in the literature were determined. Each deviation was related to the VAS score. RESULTS: Two ratios and 3 angles had a significant negative correlation with the VAS scores, indicating that beautiful faces have less deviation from the ideal target than less beautiful faces. Together, these variables explained 28.7% of the variance. CONCLUSIONS: Few "ideal" ratios and angles have a significant relationship with facial esthetics in adolescents.

Implantation of tissue-engineered mucosal substitutes in the dog palate.

Tissue shortage complicates the surgery of cleft palate (CP) anomalies. The healing of defects on the palate impairs growth of the dento-maxillary complex due to scar tissue formation. Implantation of grafts into the wound area might reduce this adverse effect of surgery. The aim of this study was to evaluate a cultured autologous mucosal substitute, which can be used as a graft material. Two different types of cultured mucosal substitutes composed of skin-derived substrates (unprocessed dermis and AlloDerm) and autologous oral keratinocytes were implanted in palatal wounds in six beagle dogs (1-1.5 years of age). The cultured substitutes were compared with a sham and a control group. The animals were sacrificed in pairs 1, 3, and 12 weeks after surgery. Epithelial regeneration, inflammatory response (leucocyte protein L1), ingrowth of (myo-) fibroblasts, collagen type III, and formation of a basal membrane (JM 403) were evaluated. The results demonstrated that all cultured substitutes possessed a multilayered epithelium, closely resembling normal palatal epithelium. After implantation, however, the epithelium was lost and an inflammatory response was observed in the first week. After 3 and 12 weeks, the implanted substitutes had completely disappeared and epithelial migration occurred from the wound margins. It is possible to culture an autologous epithelium on a skin-derived substrate and implant it as an oral mucosal substitute in palatal wounds. However, these substitutes do not improve the healing of palatal wounds. It is suggested that the revascularization of the wound area is too slow to allow survival and integration of the substitutes.