RESUMO
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.
Assuntos
Perda do Osso Alveolar , Camundongos , Animais , Feminino , Humanos , Perda do Osso Alveolar/prevenção & controle , Perda do Osso Alveolar/metabolismo , Leite , Osteoclastos/metabolismo , Osteoblastos/metabolismo , Remodelação Óssea/fisiologia , OvariectomiaRESUMO
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.
Assuntos
Reabsorção Óssea , Maxila , Animais , Camundongos , Maxila/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Endogâmicos C57BL , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Osteoclastos/metabolismo , Remodelação Óssea , Fosfatidilinositóis/metabolismoRESUMO
OBJECTIVES: To quantify survivin and NETs in synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and to assess whether there is a correlation of the quantifications with the exclusion of OA diagnosis and the activity of RA. METHODS: We performed a cross-sectional, observational study, in which 32 patients with RA and 16 with OA were included. Clinical and laboratory data were obtained, in addition to routine analysis of SF and the measurement of SF survivin and NETs. RA activity was assessed by DAS28. RESULTS: Concentrations of survivin (median, 356.9 vs. 49.9 pg/mL; p=0.0006) and NETs (median, 100.7 vs. 49.7 ng/mL; p=0.004) were elevated in the SF of the RA group compared to those of the OA group. ROC curves showed the following values for measurements of survivin and NETs: AUC of 79% and 75% respectively, with sensitivity of 75% and specificity of 78% for both. There was no correlation between survivin and NETs values for both groups, but we found association between SF survivin and serum ACPA for RA patients. CONCLUSIONS: We found an independent association between levels of survivin and NETs in SF with the exclusion of OA diagnosis, but not with RA activity. There was no correlation between survivin and NETs in SF, because we suppose that resistance to apoptosis, mediated by survivin, and NETosis are independently related to the pathophysiology of RA.
Assuntos
Artrite Reumatoide , Osteoartrite , Líquido Sinovial , Humanos , Biomarcadores , Estudos Transversais , SurvivinaRESUMO
BACKGROUND: Obesity leads to chronic low-grade inflammation, promoting detrimental effects on bone. The consumption of virgin coconut oil (VCO) is associated with benefits related to meta-inflammation. We evaluated the effect of VCO supplementation on osteopenia promoted by diet-induced obesity in mice. METHODS: Male BALB/c mice were fed a control (C) or highly refined carbohydrate-containing (HC) diet for eight weeks. After that, the HC diet group was supplemented with three doses of VCO for four weeks. RESULTS: The HC diet increased the adiposity and leptin levels associated with augmented systemic inflammatory cells improved with VCO supplementation. The HC diet reduced the trabecular bone in the tibia, lumbar vertebrae, distal and proximal femur, as well as the bone mineral density of the femur and alveolar bone. The VCO supplementation reverted bone osteopenia by increasing the trabecular bone in different sites and improving femur and alveolar bone microarchitecture. Although the reduced number of osteoblasts in the alveolar bone of the HC diet group was not significantly enhanced by VCO supplementation, the reduced Alp expression in the HC diet group was enhanced in the VCO group. These beneficial effects were associated with lowering the Rankl/Opg ratio. CONCLUSION: VCO supplementation might be an effective strategy to attenuate bone osteopenic effects induced by obesity.
RESUMO
Photobiomodulation therapy (PBMT) has been widely used to promote tissue repair. However, PBMT's critical roles in the epithelial and mesenchymal tissues interactions are still barely known. Herein, we investigated light parameters on challenged keratinocytes (KC)-i.e., cultivated under oxidative stress-solely or associated with fibroblasts (FB) in a co-culture system. Cells were treated with PBMT at the wavelength of 660 nm, at 20 mW and 0.71 W/cm2 . Three different energy densities were primarily evaluated on KC: 1 (1.4 s), 5 (7 s), and 50 J/cm2 (70 s). Next, KC and FB were co-cultured and assessed at 5 J/cm2 . This energy density was also tested in ex vivo murine skin samples. Our main data suggest that PBMT can increase cellular proliferation at low doses and cell migration in a biphasic mode (1 and 50 J/cm2 ), both further confirmed by the epidermal growth factor receptor ligand-amphiregulin-upregulation. IL-1RA mRNA-the IL-1ß (interleukin-1ß) receptor antagonist recognized to fasten wound repair-was upregulated in the co-culture system. Upon PBMT, the ex vivo findings showed a progressive increase in the epidermal thickness, although presenting qualitatively less differentiated epithelium than the control group. In conclusion, PBMT effects are dependent on the cellular interactions with the surrounding microenvironment. Ultimately, PBMT is anti-inflammatory and contributes to the expression of critical mediators of wound repair.
Assuntos
Terapia com Luz de Baixa Intensidade , Células-Tronco Mesenquimais , Animais , Fibroblastos/metabolismo , Queratinócitos , Camundongos , CicatrizaçãoRESUMO
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.
Assuntos
Polpa Dentária/citologia , Neuroglia , Pericitos , Animais , Camundongos , Nestina/genética , TransgenesRESUMO
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.
Assuntos
Resinas Compostas , Hipersensibilidade Tardia , Humanos , Resinas Compostas/uso terapêutico , Coroas , Hipersensibilidade Tardia/tratamento farmacológicoRESUMO
Mucositis is a major clinical complication associated with cancer treatment and may limit the benefit of chemotherapy. Leukocytes and inflammatory mediators have been extensively associated with mucositis severity. However, the role of eosinophils in the pathophysiology of chemotherapy-induced mucositis remains to be elucidated. Here, using GATA-1-deficient mice, we investigated the role of eosinophils in intestinal mucositis. There was marked accumulation of eosinophils in mice given irinotecan and eosinophil ablation inhibited intestinal mucositis. Treatment with Evasin-4, a chemokine receptor antagonist, reduced the recruitment of eosinophils and decreased irinotecan-induced mucositis. Importantly, Evasin-4 did not interfere negatively with the antitumour effects of irinotecan. Evasin-4 was of benefit for mice given high doses of irinotecan once Evasin-4-treated mice presented delayed mortality. Altogether, our findings suggest that Evasin-4 may have significant mucosal-protective effects in the context of antineoplastic chemotherapy and may, therefore, be useful in combination with anticancer treatment in cancer patients.
Assuntos
Antineoplásicos , Mucosite , Animais , Antineoplásicos/uso terapêutico , Camptotecina/efeitos adversos , Eosinófilos/patologia , Humanos , Mucosa Intestinal/patologia , Irinotecano/efeitos adversos , Camundongos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/patologiaRESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic analysis, we show that microRNA-132 is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium. miRNA-132 thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown of miR-132 in murine arthritis models reduces the number of osteoclasts in the joints. Clinically, RA patients express higher levels of miR-132 than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases.