Targeting phosphatidylinositol-3-kinase for inhibiting maxillary bone resorption.

Previous studies have suggested a role of phosphatidylinositol-3-kinase gamma (PI3Kγ) in bone remodeling, but the mechanism remains undefined. Here, we explored the contribution of PI3Kγ in the resorption of maxillary bone and dental roots using models of orthodontic tooth movement (OTM), orthodontic-induced inflammatory root resorption, and rapid maxillary expansion (RME). PI3Kγ-deficient mice (PI3Kγ-/- ), mice with loss of PI3Kγ kinase activity (PI3KγKD/KD ) and C57BL/6 mice treated with a PI3Kγ inhibitor (AS605240) and respective controls were used. The maxillary bones of PI3Kγ-/- , PI3KγKD/KD , and C57BL/6 mice treated with AS605240 showed an improvement of bone quality compared to their controls, resulting in reduction of the OTM and RME in all experimental groups. PI3Kγ-/- mice exhibited increased root volume and decreased odontoclasts counts. Consistently, the pharmacological blockade or genetic deletion of PI3K resulted in increased numbers of osteoblasts and reduction in osteoclasts during OTM. There was an augmented expression of Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (Alp), a reduction of interleukin-6 (Il-6), as well as a lack of responsiveness of receptor activator of nuclear factor kappa-Β (Rank) in PI3Kγ-/- and PI3KγKD/KD mice compared to control mice. The maxillary bones of PI3Kγ-/- animals showed reduced p-Akt expression. In vitro, bone marrow cells treated with AS605240 and cells from PI3Kγ-/- mice exhibited significant augment of osteoblast mineralization and less osteoclast differentiation. The PI3Kγ/Akt axis is pivotal for bone remodeling by providing negative and positive signals for the differentiation of osteoclasts and osteoblasts, respectively.

Nestin and NG2 transgenes reveal two populations of perivascular cells stimulated by photobiomodulation.

Pericytes and glial cells are known to collaborate in dental pulp tissue repair. Cell-based therapies that stimulate these stromal components may be of therapeutic relevance for partially vital dental pulp conditions. This study aimed to examine the early effect of photobiomodulation (PBM) in pericytes from experimentally injured pulp tissue. To accomplish this, we used the Nestin-GFP/NG2-DsRed mice, which could allow the identification of distinct pericyte phenotypes. We discovered the presence of two pericytes subsets within the dental pulp, the Nestin + NG2+ (type-2) and Nestin- NG2+ (type-1). Upon injury, PBM treatment led to a significant increase in Nestin+ cells and pericytes. This boost was mainly conferred by the more committed pericyte subset (NestinNG2+ ). PBM also stimulated terminal blood vessels sprouting adjacent to the injury site while maintaining signs of pulp vitality. In vitro, PBM induced VEGF upregulation, improved dental pulp cells proliferation and migration, and favored their mineralization potential. Herein, different subsets of perivascular cells were unveiled in the pulp tissue. PBM enhanced not only NG2+ cells but nestin-expressing progenitors in the injured dental pulp.

Type IV hypersensitivity associated with restorative materials: Clinical report and systematic literature review.

STATEMENT OF PROBLEM: Type IV hypersensitivity reactions (Type IV HR) are immune responses mediated by antigen-specific effector T cells. PURPOSE: The purpose of this clinical report and systematic review was to report the clinicopathological features of Type IV HR in the oral mucosa and to present a systematic literature review of case reports and case series of individuals with Type IV HR in the oral mucosa related to contact with dental materials. MATERIAL AND METHODS: The presented clinical lesions were melanotic macules with burning that affected the internal labial mucosa in contact with composite resin veneer crowns. Histopathological and immunohistochemical analysis of the lesion was performed. The systematic literature review was performed based on a search in 4 electronic databases (PubMed/MEDLINE, Scopus, Web of Science, and Ovid). RESULTS: Immunohistochemistry showed positivity for CD4, CD8, CD20, CD3, tryptase, and CD117. After conservative treatment, the patient reported improvement of symptoms, and a decrease in the number of inflammatory cells was verified. Twenty-one articles were included in the review. Unlike the present patient, the authors of all the articles recommended radical treatment with the removal of the dental material. CONCLUSIONS: Type IV HR in oral mucosa is rare, and the assessment of clinical and histopathological characteristics is essential to perform an accurate diagnosis and provide appropriate treatment.

Clinical and microbiological effects of non-surgical periodontal treatment in individuals with rheumatoid arthritis: a controlled clinical trial.

The effect of periodontal treatment on clinical, microbiological and serological parameters of patients with rheumatoid arthritis (RA) are scarce and controversial. The aim of this study was to investigate the influence of non-surgical periodontal treatment on clinical periodontal status, subgingival bacterial levels of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and RA activity through a controlled clinical trial on individuals with RA and periodontitis (PE). From a convenience sample, 107 individuals were considered eligible and consecutively allocated in four groups: (1) individuals without PE and RA (- PE-RA, n = 30); (2) individuals without PE and with RA (- PE + RA, n = 23); (3) individuals with PE and RA (+ PE + RA, n = 24); and (4) individuals with PE and without RA (+ PE-RA, n = 30). Full-mouth periodontal clinical examinations, microbiological analysis and Disease Activity Score (DAS-28) evaluations were performed at baseline (T1) and 45 days after non-surgical periodontal treatment (T2). At T1, individuals + PE + RA showed greater severity of PE than + PE-RA individuals. At T2, significant reductions were observed in all periodontal clinical parameters in both groups (p < 0.001) with a significant reduction in DAS-28 in + PE + RA (p = 0.011). Individuals + PE-RA and + PE-RA showed significant reductions for all bacteria (p < 0.001). Additionally, P. gingivalis demonstrated an expressively significant reduction in + PE + RA (p < 0.001). Non-surgical periodontal treatment was effective on improving the clinical periodontal condition, improving the RA clinical status and reducing the presence of periodontal pathogens. Brazilian Registry of Clinical Trials (ReBEC) protocol #RBR-8g2bc8 ( https://www.ensaiosclinicos.gov.br/rg/RBR-8g2bc8/ ).

Immunological signatures in saliva of systemic lupus erythematosus patients: influence of periodontal condition.

OBJECTIVES: The immune system has an important role in the development of systemic lupus erythematosus (SLE) and chronic periodontitis (CP). Altered cytokines levels characterise both diseases and contributes to periodontal tissue damage in CP and to macrocomplexes deposition with connective tissue destruction in SLE. This study aimed to evaluate the production of salivary cytokines in patients with SLE and its association with periodontal status. METHODS: The sample comprised 70 SLE patients and 70 paired controls. SLE activity and damage were scored using Systemic Lupus Erythematosus Disease Activity Index 2000 and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Subjects were classified as without or with CP. Salivary concentrations of IL-33, MMP2/TIMP2, RANK and OPG were measured by ELISA, while IL-2, IFNγ, TNFα, IL-4, IL-6, IL-10 and IL-17A were determined by Cytometric Bead Array. Linear regression models analysed association among SLE, CP and salivary cytokines. RESULTS: IL-6 and IL-17A concentrations were significantly higher in SLE/CP patients than controls/CP. Concentrations of IL-6, IL-17A and IL-33 were increased in SLE/CP individuals when compared to SLE without CP. Multivariate model revealed association of cumulative dose of corticoids with periodontal damage and of IL-33 salivary concentration with SLE activity. CONCLUSIONS: Our findings suggest that long-term therapy with corticoids would contribute with periodontal destruction in SLE patients. Moreover, the increased levels of IL-6, IL-17A and IL-33 in saliva of SLE subjects with CP may signal it as possible inflammatory pathways in this process.

ST2 regulates bone loss in a site-dependent and estrogen-dependent manner.

Interleukin-33 (IL-33) and its receptor, ST2, are implicated in bone remodeling. The lack of estrogen after menopause results in an accelerated bone loss. Here we investigated the role of ST2 in the bone loss induced by estrogen deficiency. ST2-deficient mice (ST2-/- ) and their littermates (wildtype [WT]) were ovariectomized (OVX), while ovary-intact mice were used as controls. Bone sites were analyzed by microcomputed tomography, histomorphometry, and quantitative real-time polymerase chain reaction (qPCR). Deletion of IL-33 or ST2 resulted in a similar bone loss in the femur and maxilla. Ovariectomy in WT mice caused bone loss in the same areas. The lack of ST2 in OVX mice did not alter bone remodeling in the femur but prevented bone loss in the maxilla. Consistently, ovariectomy increased the IL-33 messenger RNA (mRNA) levels in the maxilla but not in the femur. Under mechanical stimulation, ovariectomy and ST2 deletion independently increased bone remodeling induced by orthodontic tooth movement, which was also associated with a greater number of osteoclasts and a reduced number of osteoblasts in the maxillary bone. ST2-/- OVX mice, however, displayed twice as many osteoblasts as that of WT OVX mice. Ovariectomy and ST2 deletion differently altered the cytokine mRNA levels in the maxilla. Remarkably, interleukin-10 expression was decreased in both WT OVX and ST2-/- mice, and this reduction was completely restored in ST2-/- OVX mice. The results demonstrate that estrogen and IL33/ST2 independently protect against bone loss. However, the ovariectomy-induced bone loss is IL-33/ST2-dependent in the maxilla but not in the femur, indicating a bimodal and site-specific role of ST2 in bone remodeling.

Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection.

Alveolar bone loss is a result of an aggressive form of periodontal disease (PD) associated with Aggregatibacter actinomycetemcomitans (Aa) infection. PD is often observed with other systemic inflammatory conditions, including arthritis. Melanocortin peptides activate specific receptors to exert antiarthritic properties, avoiding excessing inflammation and modulating macrophage function. Recent work has indicated that melanocortin can control osteoclast development and function, but whether such protection takes place in infection-induced alveolar bone loss has not been investigated. The purpose of this study was to evaluate the role of melanocortin in Aa-induced PD. Mice were orally infected with Aa and treated with the melanocortin analog DTrp8-γMSH or vehicle daily for 30 d. Then, periodontal tissue was collected and analyzed. Aa-infected mice treated with DTrp8-γMSH presented decreased alveolar bone loss and a lower degree of neutrophil infiltration in the periodontium than vehicle-treated animals; these actions were associated with reduced periodontal levels of TNF-α, IFN-γ, and IL-17A. In vitro experiments with cells differentiated into osteoclasts showed that osteoclast formation and resorptive activity were attenuated after treatment with DTrp8-γMSH. Thus, melanocortin agonism could represent an innovative way to tame overexuberant inflammation and, at the same time, preserve bone physiology, as seen after Aa infection.-Madeira, M. F. M., Queiroz-Junior, C. M., Montero-Melendez, T., Werneck, S. M. C., Corrêa, J. D., Soriani, F. M., Garlet, G. P., Souza, D. G., Teixeira, M. M., Silva, T. A., Perretti, M. Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection.

The role of 5-lipoxygenase in Aggregatibacter actinomycetemcomitans-induced alveolar bone loss.

AIM: Leukotrienes (LTs) are pro-inflammatory lipid mediators formed by the enzyme 5-lipoxygenase (5-LO). The involvement of 5-LO metabolites in periodontal disease (PD) is not well defined. This study aimed to assess the role of 5-LO in experimental PD induced by Aggregatibacter actinomycetemcomitans (Aa). MATERIAL AND METHODS: In vivo experiments were carried out using SV129 wild-type (WT) and 5-LO-deficient (5lo-/- ) mice inoculated with Aa. Osteoclasts were stimulated in vitro with AaLPS in the presence or not of selective inhibitors of the 5-LO pathway, or LTB4 or platelet-activating factor (PAF), as PAF has already been shown to increase osteoclast activity. RESULTS: In 5lo-/- mice, there were no loss of alveolar bone and less TRAP-positive osteoclasts in periodontal tissues, after Aa inoculation, despite local production of TNF-α and IL-6. The differentiation and activity of osteoclasts stimulated with AaLPS were diminished in the presence of BLT1 antagonist or 5-LO inhibitor, but not in the presence of cysteinyl leukotriene receptor antagonist. The osteoclast differentiation induced by PAF was impaired by the BLT1 antagonism. CONCLUSION: In conclusion, LTB4 but not CysLTs is important for Aa-induced alveolar bone loss. Overall, LTB4 affects osteoclast differentiation and activity and is a key intermediate of PAF-induced osteoclastogenesis.

Dental management for patients undergoing heart valve surgery.

This study sought to review current guidelines and the most optimal dental management for patients undergoing cardiac valve surgery.

Association between periodontal disease and inflammatory arthritis reveals modulatory functions by melanocortin receptor type 3.

Because there is clinical evidence for an association between periodontal disease and rheumatoid arthritis, it is important to develop suitable experimental models to explore pathogenic mechanisms and therapeutic opportunities. The K/BxN serum model of inflammatory arthritis was applied using distinct protocols, and modulation of joint disruption afforded by dexamethasone and calcitonin was established in comparison to the melanocortin (MC) receptor agonist DTrp(8)-γ-melanocyte stimulating hormone (MSH; DTrp). Wild-type and MC receptor type 3 (MC3)-null mice of different ages were also used. There was significant association between severity of joint disease, induced with distinct protocols and volumes of the arthritogenic K/BxN serum, and periodontal bone damage. Therapeutic treatment with 10 µg dexamethasone, 30 ng elcatonin, and 20 µg DTrp per mouse revealed unique and distinctive pharmacological properties, with only DTrp protecting both joint and periodontal tissue. Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r(-/-) compared with wild-type mice, with significant exacerbation at 14 weeks of age. These data reveal novel protective properties of endogenous MC3 on periodontal status in health and disease and indicate that MC3 activation could lead to the development of a new genus of anti-arthritic bone-sparing therapeutics.

The association of openness personality trait with stress-related salivary biomarkers in burning mouth syndrome.

BACKGROUND: Burning mouth syndrome (BMS) is a chronic disorder defined as a burning sensation in the oral mucosa without evidence of pathological findings. Its pathophysiology is largely unknown, but psychiatric disorders and personality traits have been implicated. OBJECTIVE: This study investigated whether there is any association between salivary biomarkers and personality traits in BMS patients. METHODS: It was a cross-sectional, controlled study that evaluated 30 individuals with BMS and 32 controls. All subjects were assessed with a structured psychiatric interview (Mini International Neuropsychiatric Interview) and the Big Five inventory. Salivary levels of brain-derived neurotrophic factor (BDNF), neural growth factor, tumor necrosis factor-α, interleukin (IL)-6, IL-10 and cortisol were determined. RESULTS: We found that BMS patients exhibited more traits of neuroticism and lower openness than controls. Openness showed a moderate and negative correlation with cortisol, BDNF and IL-6. CONCLUSION: Personality traits are associated with salivary biomarkers in BMS.

Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients.

BACKGROUND AND OBJECTIVE: Oral mucositis (OM) is considered a painful and debilitating side effect in patients receiving head and neck cancer treatment. Low-level laser therapy (LLLT) proved to be effective to prevent and treat chemoradiotherapy-induced OM. The aim of this study was to evaluate the effect of LLLT in the severity of OM in patients with head and neck cancer and on the release of salivary inflammatory mediators. Clinical (score of OM severity) and biochemical parameters (concentration of inflammatory mediators, growth factors, and enzymes in saliva) were used. MATERIALS AND METHODS: Thirty patients were randomized into two groups: control and laser. LLLT was performed three times a week in the laser group, while control group received sham irradiation. OM severity was assessed according to the World Health Organization (WHO) and National Cancer Institute (NCI) scales. Pro-inflammatory and anti-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-10, TGF-ß), growth factors (EGF, FGF, VEGF), and metalloproteinases (MMP2/TIMP2, MMP9/TIMP2) concentrations were assessed using ELISA test. Saliva samples were collected on admission, and at the 7th, 21st, and 35th sessions of radiotherapy. RESULTS: The laser group showed a reduction in the severity of OM, which coursed with significantly diminished salivary concentration of EGF and VEGF in the 7th radiotherapy session and of IL-6 and FGF in the 35th. There was a trend for reduced levels of IL-1ß, TNF-α, IL-10, TGF-ß, MMP2/TIMP2, MMP9/TIMP2 in the laser group compared to the control, however, no statistically significant differences were found. CONCLUSIONS: These findings demonstrated that LLLT was effective in reducing the severity of chemoradiotherapy-induced OM and was associated with the reduction of inflammation and repair.

Protective Effect of Bovine Milk Extracellular Vesicles on Alveolar Bone Loss.

SCOPE: Bovine milk extracellular vesicles (MEVs) have demonstrated therapeutic potential in regulating bone cell activity. However, the outcome of their use on alveolar bone loss has not yet been demonstrated. METHODS AND RESULTS: This study evaluates the effect of oral administration of MEVs on ovariectomized (OVX) mice. There is a reduced height of the alveolar bone crest in OVX mice by MEVs treatment, but the alveolar bone parameters are not altered. OVX mice are then submitted to a force-induced bone remodeling model by orthodontic tooth movement (OTM). MEVs-treated mice have markedly less bone remodeling movement, unlike the untreated OVX mice. Also, OVX mice treated with MEVs show an increased number of osteoblasts and osteocytes associated with higher sclerostin expression and reduce osteoclasts in the alveolar bone. Although the treatment with MEVs in OVX mice does not show differences in root structure in OTM, few odontoclasts are observed in the dental roots of OVX-treated mice. Compared to untreated mice, maxillary and systemic RANKL/OPG ratios are reduced in OVX mice treated with MEVs. CONCLUSION: Treatment with MEVs results in positive bone cell balance in the alveolar bone and dental roots, indicating its beneficial potential in treating alveolar bone loss in the nutritional context.

Burning mouth syndrome: a therapeutic approach involving mechanical salivary stimulation.

OBJECTIVE: The study aimed to evaluate the effects of salivary stimulation therapy on the salivary flow, quality of saliva, and symptoms in patients with burning mouth syndrome (BMS). BACKGROUND: BMS is a chronic disorder characterized by a burning sensation. Some reports have proposed a role for saliva in the pathogenesis of BMS. METHODS: Twenty-six BMS patients underwent treatment with salivary mechanical stimulation. Resting and stimulated saliva were collected before and after therapy. Salivary levels of total protein, brain-derived neurotrophic factor, interleukin-10, tumor necrosis factor-α, interleukin-6, and nerve growth factor were assessed before and 90 days after therapy by enzyme-linked immunosorbent assay. RESULTS: A significant reduction in the burning sensation and number of burning sites as well as an improvement of taste disturbances and xerostomia were observed after therapy. The salivary flow was not significantly modified. However, the therapy resulted in a significant decrease in salivary levels of total protein and an increase of tumor necrosis factor-α. CONCLUSION: Salivary mechanical stimulation therapy is effective in reducing clinical symptoms of BMS.

Hemorrhagic complications in individuals with liver disease submitted to minor oral surgery.

Individuals with chronic liver disease (CLD) have an increased risk of bleeding from thrombocytopenia and changes in hemostasis. The aim of this study was to evaluate the frequency of and the factors associated with the occurrence of bleeding in CLD patients who underwent dental surgical procedures. This was a retrospective study whose data were collected in a hospital dentistry service between 2010 and 2016. The patients were referred from the gastroenterology and liver transplantation services of a university hospital for dental treatment. The study followed the STROBE guidelines. Among the 71 surgical procedures performed, there were 17 (24%) perioperative and postoperative bleeding episodes, 14 of which were in pretransplant patients and 11 received blood transfusion before dental surgery. Individuals with a previous history of bleeding (PR = 2.67, CI = 1.07-6.67, P  = 0.035) and those with a platelet count before surgery 50 × 10 9 /l or less (PR = 7.48, CI = 1.70-32.86, P  = 0.008) had a higher prevalence of perioperative and postoperative bleeding episodes than their peers without a previous history of bleeding, and those with platelet count greater than 50 × 10 9 /l. The approach to individuals with CLD is complex and represents a challenge to the clinician. A careful anamnesis combined with laboratory screening of coagulation disorders appears to be useful to identify individuals at a major risk of bleeding. Studies identifying the predisposing factors of bleeding in CLD patients support well tolerated protocols for oral surgery in this group.

The impact of burning mouth syndrome on health-related quality of life.

BACKGROUND: Burning mouth syndrome is a chronic disorder that is characterized by a burning sensation and a normal clinical appearance of the oral mucosa. This condition often affects the health-related quality of life in patients. As such, the aim of this study was to compare the health-related quality of life of patients with BMS and healthy controls, using the validated Portuguese versions of the SF-36 and OHIP-49 questionnaires. METHODS: A calculated sample of Brazilian patients with BMS (n = 26) was compared with a control group (n = 27), paired for gender and age. Sociodemographic information and clinical characteristics were obtained, and interviews were conducted using the SF-36 and OHIP-49. To evaluate the normality of the variables, we used the Kolmogorov-Smirnov test. The chi-square test, Fisher exact test and Mann-Whitney U-Test were used to compare sociodemographic and clinical characteristics of individuals with BMS and controls Mann-Whitney U-test were carried out to compare SF-36 and OHIP-49 between BMS patients and controls. The significance level was set at 0.05. To compare the dimensions of the SF-36 and OHIP-49 between BMS patients and controls, we considered Bonferroni correction. So for comparison of the dimensions, the significance level was set at 0.00625 for SF-36 and at 0.00714 for OHIP-49. RESULTS: The clinical and demographic data were similar in both groups (P > 0.05). SF-36 scores were significantly lower in all domains for patients with BMS (P < 0.00625). OHIP-49 scores were higher for individuals with BMS (P < 0.00714). CONCLUSIONS: BMS has a negative impact on the health-related quality of life of individuals, as can be shown by instruments such as the SF-36 and OHIP-49. So, the evaluation of quality of life might be useful for more information about the nature and severity of BMS, to evaluate the effects of treatment protocols, in order to improve their outcomes by means a humanized clinical practice.

Effect of diabetes on orthodontic tooth movement in a mouse model.

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading. Type 1 diabetes results in bone remodeling, suggesting that this disease might affect orthodontic tooth movement. The present study investigated the effects of the diabetic state on orthodontic tooth movement. An orthodontic appliance was placed in normoglycemic (NG), streptozotocin-induced diabetes (DB), and insulin-treated DB (IT) C57BL6/J mice. Histomorphometric analysis and quantitative PCR of periodontium were performed. The DB mice exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphate (TRAP) -positive osteoclasts than NG mice. This was associated with increased expression of factors involved in osteoclast activity and recruitment (Rankl, Csf1, Ccl2, Ccl5, and Tnfa) in DB mice. The expression of osteoblastic markers (Runx2, Ocn, Col1, and Alp) was decreased in DB mice. Reversal of the diabetic state by insulin treatment resulted in morphological findings similar to those of NG mice. These results suggest that the diabetic state up-regulates osteoclast migration and activity and down-regulates osteoblast differentiation, resulting in greater orthodontic tooth movement.

Direct oral anticoagulants in oral surgery: a prospective cohort.

BACKGROUND: Quantitative assessment of bleeding in dental extractions is rarely reported in the literature. The assessment of bleeding might provide additional evidence to predict and minimize postoperative outcomes. The aim of this study was to evaluate the pattern of bleeding in individuals taking direct oral anticoagulants (DOACs) submitted to dental extractions. METHODS: Intraoperative bleeding was evaluated by using total collected bleeding corrected by absorbance reading (dental bleeding score). To monitoring bleeding episodes from the day of surgery, this cohort was followed up until the seventh postoperative day. RESULTS: Forty-five procedures were performed in three comparative groups, patients under DOACs, individuals taking vitamin K antagonists (VKAs) and without anticoagulant therapy. No bleeding events were observed in procedures carried out in individuals of the DOAC group. Additional hemostatic measures were required in two procedures in the VKA group and one in the non-anticoagulated group. The dental bleeding scores obtained for the DOAC and VKA groups were similar. CONCLUSIONS: Our data suggest that the DOAC therapy did not result in increased bleeding outcomes in this sample.

Aerobic and resistance training improve alveolar bone quality and interferes with bone-remodeling during orthodontic tooth movement in mice.

The direct effects of physical activity on long bones are already recognized. However, little information is available regarding distant osseous sites, such as maxillary bone. We evaluated the influence of physical training on alveolar bone quality, with and without mechanically-induced load during orthodontic tooth movement in mice. Forty-two C57BL/6 mice were divided into sedentary, resistance and aerobic training groups. Training period lasted for eight weeks and mechanical loads (orthodontic tooth movement - OTM) were applied during the last 14 days of training. Both types of training enhanced the quality of maxillary bone, increasing bone mineral density (BMD), trabecular bone volume (BV) and bone volume/total volume ratio (BV/TV). OTM significantly reduced in trained groups. Consistently, the number of osteoblasts increased whereas the number of osteoclasts decreased on the OTM side in trained groups in comparison to the sedentary group. IGF-1, RUNX2 and OPG genes expression were also increased. The RANKL/OPG ratio and IL-6 expression were reduced in the maxillary bone. Similar results were verified in the femoral bone. In line with these findings, physical training resulted in a decrease of osteoclast differentiation from femoral bone marrow; as well as the force required to fracture the tibia of trained animals increased. Physical training also caused EDL muscle hypertrophy and increased expression of IGF-1 and IGF-1/Myostatin ratio in the gastrocnemius muscle, whereas FNDC5 gene expression was similar among groups in femur, but decreased in alveolar bone submitted to OTM. In conclusion, physical training increased bone quality, not only on long bones, but also in a distant site such as the maxilla. Differences were more evident in the course of maxillary mechanical loading. Mechanisms involve systemic and local effects on bone cells and target molecules as RANKL, OPG, IL-6 and IGF-1.