ABSTRACT
Abstract Lipoproteins are important bacterial immunostimulating molecules capable of inducing receptor activator of nuclear factor-κB (RANKL) and osteoclast formation in vitro and in vivo . Although these molecules are present in periodontopathogenic bacteria, their role in periodontitis is not known. In this study, we used Pam2CSK4 (PAM2), a synthetic molecule that mimics bacterial lipoprotein, to investigate the effects of lipoproteins on periodontitis in mice. C57BL/6 male mice were randomly divided into three experimental groups: 1) Negative control group: animals received vehicle injection; 2) Positive control group: animals received injection of Escherichia coli lipopolysaccharide (LPS); 3) PAM2 group: animals received PAM2 injection. All the injections were performed bilaterally every other day into the palatal mucosa between first and second molars. After twenty-four days, the animals were euthanized to assess alveolar bone volume (micro-CT), cellular and extracellular composition in the gingiva (stereometric analysis), and osteoclast numbers (TRAP staining). Treatment with either PAM2 or LPS induced gingival inflammation, as demonstrated by increased infiltration of inflammatory cells and enhanced angiogenesis, associated with a smaller number of fibroblasts and decreased extracellular matrix. Importantly, treatment not only with LPS but also with PAM2 resulted in a larger number of TRAP+ multinucleated osteoclasts and significant loss of alveolar bone. Collectively, our data demonstrate that PAM2 can induce gingival inflammation and bone loss in mice, broadening the avenues of investigation into the role of lipoproteins in the pathogenesis of periodontal disease.
Subject(s)
Animals , Male , Periodontitis/etiology , Periodontitis/pathology , Toll-Like Receptor 2/antagonists & inhibitors , Lipopeptides/pharmacology , Osteoclasts/drug effects , Periodontitis/microbiology , Time Factors , Random Allocation , Alveolar Bone Loss/etiology , Alveolar Bone Loss/pathology , Disease Models, Animal , X-Ray Microtomography , Alveolar Process/drug effects , Alveolar Process/pathology , Tartrate-Resistant Acid Phosphatase , Gingiva/drug effects , Gingiva/pathology , Gingivitis/etiology , Gingivitis/pathology , Mice, Inbred C57BLABSTRACT
Abstract Lipoproteins are important bacterial immunostimulating molecules capable of inducing receptor activator of nuclear factor-κB (RANKL) and osteoclast formation in vitro and in vivo . Although these molecules are present in periodontopathogenic bacteria, their role in periodontitis is not known. In this study, we used Pam2CSK4 (PAM2), a synthetic molecule that mimics bacterial lipoprotein, to investigate the effects of lipoproteins on periodontitis in mice. C57BL/6 male mice were randomly divided into three experimental groups: 1) Negative control group: animals received vehicle injection; 2) Positive control group: animals received injection of Escherichia coli lipopolysaccharide (LPS); 3) PAM2 group: animals received PAM2 injection. All the injections were performed bilaterally every other day into the palatal mucosa between first and second molars. After twenty-four days, the animals were euthanized to assess alveolar bone volume (micro-CT), cellular and extracellular composition in the gingiva (stereometric analysis), and osteoclast numbers (TRAP staining). Treatment with either PAM2 or LPS induced gingival inflammation, as demonstrated by increased infiltration of inflammatory cells and enhanced angiogenesis, associated with a smaller number of fibroblasts and decreased extracellular matrix. Importantly, treatment not only with LPS but also with PAM2 resulted in a larger number of TRAP+ multinucleated osteoclasts and significant loss of alveolar bone. Collectively, our data demonstrate that PAM2 can induce gingival inflammation and bone loss in mice, broadening the avenues of investigation into the role of lipoproteins in the pathogenesis of periodontal disease.
Subject(s)
Animals , Male , Periodontitis/etiology , Periodontitis/pathology , Toll-Like Receptor 2/antagonists & inhibitors , Lipopeptides/pharmacology , Osteoclasts/drug effects , Osteoclasts/physiology , Periodontitis/microbiology , Time Factors , Random Allocation , Alveolar Bone Loss/etiology , Alveolar Bone Loss/pathology , Disease Models, Animal , X-Ray Microtomography , Alveolar Process/drug effects , Alveolar Process/pathology , Tartrate-Resistant Acid Phosphatase , Gingiva/drug effects , Gingiva/pathology , Gingivitis/etiology , Gingivitis/pathology , Mice, Inbred C57BLABSTRACT
Abstract The present study aimed to investigate the use of platelet-rich plasma (PRP) on tooth extraction sites in rats treated with bisphosphonates. Thirty Albinus Wistar male rats were administered 0.035 mg/kg zoledronic acid intravenously for 8 weeks, divided into four administrations with a 2-week interval between each application, after which their upper right central incisors were extracted to induce the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The samples were divided into the following two groups: Group 1 (G1) underwent marginal resection of BRONJ followed by the use of PRP, while Group 2 (G2) underwent resection of BRONJ but without the use of PRP. The treatment groups were evaluated after 14, 28, and 42 days. Clinical, microtomographic, microscopic, and immunohistochemical (IHC) evaluations were performed. Microtomography results revealed no significant difference between the groups (p <0.05) in any time period. Histomorphometric analysis showed increased bone formation over time for both groups (p < 0.001). G1 demonstrated a greater amount of new bone formation than G2 at 28 and 42 days (p < 0.001), with G1 presenting greater vascularization and a slightly higher VEGF expression. For both groups, RANKL/OPG expression levels were sufficient as a parameter for indicating the rate of bone remodeling in a previously treated area of osteonecrosis groups. Taken together, our findings indicated that the use of PRP improves the resolution process of BRONJ.
Subject(s)
Animals , Male , Rats , Diphosphonates/therapeutic use , Bone Density Conservation Agents/therapeutic use , Platelet-Rich Plasma , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy , Osteoclasts/drug effects , Tooth Extraction/adverse effects , Wound Healing , Rats, Wistar , Disease Models, Animal , Bisphosphonate-Associated Osteonecrosis of the Jaw/physiopathology , Bisphosphonate-Associated Osteonecrosis of the Jaw/pathologyABSTRACT
Abstract Colchicine is widely used in the treatment of several inflammatory diseases due to its anti-inflammatory effect, but effects on bone metabolism are unclear. The aim of this study was to evaluate the effects of systemically-administered colchicine on healthy periodontium and experimentally-induced periodontitis. In total, 42 male Wistar rats were included in this study. A non-ligated group constituting the negative control group (Control, C, n = 6) and a ligature-only group forming the positive control group (LO, n = 12) were created separately. Twelve rats were treated with 0.4 mg/kg colchicine and another 12 with 1 mg/kg colchicine. In the colchicine-administered groups, right mandibles constituted the ligated groups (1 mgC-L or 0.4 mgC-L) and left mandibles formed the corresponding non-ligated controls (1mgC or 0.4mgC). Silk ligatures were placed at the gingival margin of the lower first molars. The animals were euthanized at different time-points of healing (11 or 30 days). Alveolar bone loss was clinically measured and TRAP+ osteoclasts, osteoblastic activity, and MMP-1 expression were examined histologically. There was no increase in alveolar bone loss with either colchicine dose in healthy periodontium (p > 0.05) and the highest level of alveolar bone loss, TRAP+ osteoclast number, and MMP-1 expression were measured in the LO group (p < 0.05). The 0.4 mgC-L group showed less alveolar bone loss at 11 days (p < 0.05), but greater loss at 30 days. The 1 mgC-L group showed higher osteoblast number than the other ligated groups (p < 0.05) at both time-points. In summary, colchicine did not increase alveolar bone loss in healthy periodontium and also may tend to reduce periodontitis progression. However, further extensive study is necessary to understand the mechanism of colchicine action on alveolar bone loss in periodontitis.
Subject(s)
Humans , Animals , Male , Periodontitis/drug therapy , Colchicine/pharmacology , Alveolar Bone Loss/drug therapy , Anti-Inflammatory Agents/pharmacology , Osteoblasts/drug effects , Osteoclasts/drug effects , Periodontitis/etiology , Periodontitis/pathology , Time Factors , Immunohistochemistry , Colchicine/therapeutic use , Reproducibility of Results , Alveolar Bone Loss/pathology , Treatment Outcome , Rats, Wistar , Matrix Metalloproteinase 1/analysis , Tubulin Modulators/pharmacology , Tartrate-Resistant Acid Phosphatase/analysis , Ligation , Anti-Inflammatory Agents/therapeutic useABSTRACT
Abstract Objectives This investigation aimed to assess the differentiation inhibitory effects of ProRoot MTA® (PMTA) and Biodentine® (BIOD) on osteoclasts originated from murine bone marrow macrophages (BMMs) and compare these effects with those of alendronate (ALD). Materials and Methods Mouse BMMs were cultured to differentiate into osteoclasts with macrophage colony-stimulating factor and receptor activator of NF-κB (RANKL), treated with lipopolysaccharide. After application with PMTA, BIOD, or ALD, cell toxicities were examined using WST-1 assay kit, and RANKL-induced osteoclast differentiation and activities were determined by resorption pit formation assay and tartrate-resistant acid phosphate (TRAP) staining. The mRNA levels of osteoclast activity-related genes were detected with quantitative real time polymerase chain reaction. Expressions of molecular signaling pathways were assessed by western blot. All data were statistically analyzed with one-way ANOVA and Tukey's post-hoc test (p<0.05). Results Mouse BMMs applied with PMTA, BIOD, or ALD showed highly reduced levels of TRAP-positive osteoclasts. The BIOD treated specimens suppressed mRNA expressions of cathepsin K, TRAP, and c-Fos. Nonetheless, it showed a lower effect than PMTA or ALD applications. Compared with ALD, PMTA and BIOD decreased RANKL-mediated phosphorylation of ERK1/2 and IκBα. Conclusions PMTA and BIOD showed the inhibitory effect on osteoclast differentiation and activities similar to that of ALD through IκB phosphorylation and suppression of ERK signaling pathways.
Subject(s)
Animals , Mice , Osteoclasts/drug effects , Root Canal Filling Materials/pharmacology , Bone Marrow Cells/drug effects , Cell Differentiation/drug effects , Silicates/pharmacology , Calcium Compounds/pharmacology , Alendronate/pharmacology , Bone Density Conservation Agents/pharmacology , Osteoclasts/physiology , Osteogenesis/drug effects , Phosphorylation/drug effects , Root Resorption/prevention & control , Time Factors , Bone Marrow Cells/cytology , Cell Survival/drug effects , Cells, Cultured , Blotting, Western , Reproducibility of Results , MAP Kinase Signaling System/drug effects , I-kappa B Proteins/drug effects , RANK Ligand/analysis , RANK Ligand/drug effects , Real-Time Polymerase Chain Reaction , Tartrate-Resistant Acid PhosphataseABSTRACT
Resveratrol in cell culture media increases osteoblastic markers. Also results from previous studies provide evidence for resveratrol positive effects on bone healing and bone production. In this preclinical study we investigated bone healing in rats by resveratrol systemic application. 30 Wistar male rats were divided into two groups (study group and control group). At first, maxillary second molars of rats were extracted. The rats were kept in laboratory for next 28 days. Study group received resveratrol 20 mg/kg by abdominal injection every day. The control group received placebo in the same manner that study group. Rats were sacrificed after 28 days and bone samples were collected from center of maxillary second molar socket. Samples were evaluated histologically for new bone formation, inflammation, necrosis, fibrosis and foreign body reaction. The mean difference of new bone formation in control group (28.30 %) and study group (45 %) were statistically significant (P=0.014). There were no significant differences in inflammation, fibrosis, necrosis and foreign body reaction (P>0.05). Resveratrol has positive effects on bone healing but more evidence needed from more clinical and animal studies.
El resveratrol en los medios de cultivo celular aumenta los marcadores osteoblásticos. Los resultados de estudios anteriores proporcionan evidencia de efectos positivos del resveratrol sobre la curación ósea y la producción ósea. En este estudio preclínico, investigamos la curación ósea en ratas mediante la aplicación sistémica de resveratrol. Se dividieron 30 ratas macho Wistar en dos grupos (estudio y control). Inicialmente se extrajeron los segundos molares maxilares de las ratas y los animales se mantuvieron en el laboratorio durante los siguientes 28 días. El grupo de estudio recibió todos los días resveratrol 20 mg/kg por inyección abdominal . El grupo control recibió placebo de la misma manera que el grupo estudio. Las ratas fueron sacrificadas después de 28 días y se recogieron muestras de hueso del centro del segundo molar maxilar. Las muestras se evaluaron histológicamente para la formación de hueso nuevo, inflamación, necrosis, fibrosis y reacción de cuerpo extraño. La media de formación de hueso nuevo en el grupo control (28,30 %) y en el grupo estudio (45 %) fueron estadísticamente significativas (P=0,014). No hubo diferencias significativas en la inflamación, fibrosis, necrosis y reacción al cuerpo extraño (P>0,05). El resveratrol tiene efectos positivos sobre la curación de los huesos, pero aún es necesario realizar más pruebas de estudios clínicos, como también en animales.
Subject(s)
Animals , Rats , Osteoblasts/drug effects , Osteoclasts/drug effects , Stilbenes/pharmacology , Bone Development/drug effects , Osteogenesis/drug effects , Rats, Wistar , Dietary SupplementsABSTRACT
Statins are a widely prescribed class of medications that inhibit similar pathways as the anti-resorptive bisphosphonate drugs. Statins target the mevalonate pathway by blocking HMG-CoA reductase. Several recent meta-analyses concluded statins are osteoprotective in the general population. Here we present current literature exploring the mechanisms underlying the putative osteoprotective effects of statins. We also review recent clinical studies, ranging from observational cohort studies to randomized clinical trials, testing the effect of statins on bone health in various populations. (AU)
Las estatinas son un grupo de drogas prescriptas en forma habitual, con la capacidad de bloquear vías de señalización similares a las inhibidas por los amino-bisfosfonatos. Las estatinas inhiben la vía del mevalonato, a través del bloqueo de diferentes enzimas. Varios metaanálisis recientes llevaron a la conclusión de que las estatinas tienen capacidad osteoprotectora en la población general. En esta revisión presentamos la literatura actual describiendo los mecanismos que subyacen en el potencial efecto osteoprotector de las estatinas, como así también estudios observacionales y clínicos aleatorizados sobre el efecto de estatinas en la salud ósea en diversas poblaciones. (AU)
Subject(s)
Humans , Animals , Male , Female , Middle Aged , Aged , Aged, 80 and over , Mice , Osteoporosis/prevention & control , Bone Density/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Osteoblasts/drug effects , Osteoclasts/drug effects , Osteoporosis/drug therapy , Bone and Bones/metabolism , Postmenopause/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , GTP-Binding Proteins/drug effects , Simvastatin/administration & dosage , Diphosphonates/therapeutic use , Diphosphonates/pharmacology , Dyslipidemias/drug therapy , Fractures, Bone/prevention & control , Atorvastatin/administration & dosage , Mevalonic Acid/pharmacologyABSTRACT
Abstract The aim of this study was to evaluate the effect of acute administration of nicotine and ethanol on tooth movement in rats. Two hundred rats were divided into eight groups: S: saline; N: nicotine; E: ethanol; NE: nicotine and ethanol; SM: saline with tooth movement; NM: nicotine with tooth movement; EM: ethanol with tooth movement; and NEM: nicotine and ethanol with tooth movement. All the solutions were applied for 32, 44, or 58 days, according to the subgroup. Orthodontic movement (25 cN) was initiated 30 days after solution administration in the groups with tooth movement. The rats were euthanized 2, 14, or 28 days after initiation of tooth movement. Tooth sections were stained using picrosirius and tartrate-resistant acid phosphatase (TRAP). The data were compared by ANOVA using Tukey's HSD and Games-Howell. On day 28 of tooth movement, the NEM group had a lower percentage of type I collagen compared to the SM group (p = 0.0448), and the S group had a higher number of osteoclasts/μm2 compared to the N group (p = 0.0405). Nicotine and ethanol did not affect the tooth movement rate, regardless of induction of orthodontic movement. Nicotine influenced the number of osteoclasts by decreasing their quantity when dental movement was not induced. When nicotine was associated with ethanol, it interfered in the maturation of collagen fibers during orthodontic movement.
Subject(s)
Animals , Male , Tooth Movement Techniques/methods , Bone Regeneration/drug effects , Bone Resorption/chemically induced , Ethanol/administration & dosage , Alveolar Process/drug effects , Nicotine/administration & dosage , Osteoclasts/drug effects , Osteogenesis/drug effects , Reference Values , Time Factors , Random Allocation , Collagen/drug effects , Rats, Wistar , Tartrate-Resistant Acid PhosphataseABSTRACT
Bone remodeling is a process regulated by the interaction between cells and various molecules such as parathyroid hormone (PTH). The aim of the study was to evaluate the effect of different doses of PTH on osteoclast activity in a culture model of bone organs. Six-day-old male C57BL/6 mice (n=14) were euthanized and the calvariae were dissected and sectioned in the middle, keeping the periosteal and endosteal. The bone fragments were divided into three groups: Group I (control - without adding PTH), Group II (addition of 3 nM PTH) and Group III (30 nM PTH), all cultured in aMEM for up to 72 h osteoclast activity was evaluated by biochemical quantification of calcium released in the culture medium at intervals of 24, 48, and 72 h and by histomorphometric analysis of bone resorption lacunae at 72 h our results show that group II exhibited significantly higher values of calcium levels in the medium compared to group I (p<0.05) in all intervals, also being higher for group III at 24 hours (p<0.05). Group II promoted a greater demineralization area (22068 ± 2193 mm2) than those found in group I (2084 ± 38 mm2) and group III (8952 ± 246 mm2), with statistically significant difference (p<0.001) among all groups. We concluded that in culture model of bone organs PTH promotes higher bone resorption when administered in lower doses.
La remodelación ósea es un proceso regulado por la interacción entre las células y varias moléculas como la hormona paratiroidea (PTH). El objetivo de este estudio fue evaluar el efecto de diferentes dosis de PTH sobre la actividad de los osteoclastos en un modelo de cultivo de órganos óseos. Se sacrificaron ratones C57BL/6 machos, de 6 días de edad (n = 14), y se disecaron y seccionaron las calvarias, manteniendo el periostio y endostio. Los fragmentos óseos se dividieron en tres grupos: Grupo I (control - sin adición de PTH), Grupo II (adición de 3 mM de PTH) y Grupo III (30 nM de PTH), todos cultivados en aMEM hasta 72 horas. La actividad de los osteoclastos se evaluó mediante la cuantificación bioquímica de calcio liberado en medio de cultivo, a intervalos de 24, 48 y 72 horas, y por análisis histomorfométrico de las lagunas de resorción ósea a las 72 horas. Nuestros resultados muestran que el grupo II exhibió valores significativamente más altos de calcio en el medio, comparado con el grupo I (p <0.05) en todos los intervalos, siendo también más alto para el grupo III a las 24 horas (p <0.05). El grupo II promovió una mayor área de desmineralización (22068 ± 2193 mm2) que los encontrados en el grupo I (2084 ± 38 mm2) y en el grupo III (8952 ± 246 mm2), con diferencia estadísticamente significativa (p <0,001) entre todos los grupos. Concluimos que en el modelo de cultivo de órganos óseos la PTH promueve una mayor resorción ósea cuando se administra en dosis más bajas.
Subject(s)
Animals , Male , Mice , Osteoclasts/drug effects , Osteoclasts/metabolism , Parathyroid Hormone/pharmacology , Bone Remodeling/drug effects , In Vitro Techniques , Mice, Inbred C57BL , Tissue Culture TechniquesABSTRACT
Abstract Objective Alendronate (ALN) inhibits osteoclastic bone resorption and triggers osteostimulative properties both in vivo and in vitro, as shown by increase in matrix formation. This study aimed to explore the efficacy of 1% ALN gel as local drug delivery (LDD) in adjunct to scaling and root planing (SRP) for the treatment of chronic periodontitis among smokers. Material and Methods 75 intrabony defects were treated in 46 male smokers either with 1% ALN gel or placebo gel. ALN gel was prepared by adding ALN into carbopol-distilled water mixture. Clinical parameters [modified sulcus bleeding index, plaque index, probing depth (PD), and periodontal attachment level (PAL)] were recorded at baseline, at 2 months, and at 6 months, while radiographic parameters were recorded at baseline and at 6 months. Defect fill at baseline and at 6 months was calculated on standardized radiographs by using the image analysis software. Results Mean PD reduction and mean PAL gain were found to be greater in the ALN group than in the placebo group, both at 2 and 6 months. Furthermore, a significantly greater mean percentage of bone fill was found in the ALN group (41.05±11.40%) compared to the placebo group (2.5±0.93%). Conclusions The results of this study showed 1% ALN stimulated a significant increase in PD reduction, PAL gain, and an improved bone fill compared to placebo gel in chronic periodontitis among smokers. Thus, 1% ALN, along with SRP, is effective in the treatment of chronic periodontitis in smokers.
Subject(s)
Humans , Male , Adult , Middle Aged , Smoking/adverse effects , Dental Scaling/methods , Alendronate/administration & dosage , Bone Density Conservation Agents/administration & dosage , Chronic Periodontitis/etiology , Chronic Periodontitis/therapy , Osteoclasts/drug effects , Time Factors , Radiography , Smoking/physiopathology , Periodontal Index , Dental Plaque Index , Reproducibility of Results , Treatment Outcome , Drug Delivery Systems , Chemotherapy, Adjuvant , Periodontal Attachment Loss , Statistics, Nonparametric , Chronic Periodontitis/physiopathology , Chronic Periodontitis/diagnostic imaging , GelsABSTRACT
Orthodontic tooth movement (OTM) is a dynamic process of bone modeling involving osteoclast-driven resorption on the compression side. Consequently, to estimate the influence of various situations on tooth movement, experimental studies need to analyze this cell. Objectives The aim of this study was to test and validate a new method for evaluating osteoclastic activity stimulated by mechanical loading based on the fractal analysis of the periodontal ligament (PDL)-bone interface. Material and Methods The mandibular right first molars of 14 rabbits were tipped mesially by a coil spring exerting a constant force of 85 cN. To evaluate the actual influence of osteoclasts on fractal dimension of bone surface, alendronate (3 mg/Kg) was injected weekly in seven of those rabbits. After 21 days, the animals were killed and their jaws were processed for histological evaluation. Osteoclast counts and fractal analysis (by the box counting method) of the PDL-bone interface were performed in histological sections of the right and left sides of the mandible. Results An increase in the number of osteoclasts and in fractal dimension after OTM only happened when alendronate was not administered. Strong correlation was found between the number of osteoclasts and fractal dimension. Conclusions Our results suggest that osteoclastic activity leads to an increase in bone surface irregularity, which can be quantified by its fractal dimension. This makes fractal analysis by the box counting method a potential tool for the assessment of osteoclastic activity on bone surfaces in microscopic examination. .
Subject(s)
Animals , Male , Rabbits , Bone Remodeling/physiology , Fractals , Osteoclasts/physiology , Periodontal Ligament/anatomy & histology , Tooth Movement Techniques/methods , Alendronate/pharmacology , Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Image Processing, Computer-Assisted , Osteoclasts/drug effects , Periodontal Ligament/physiology , Reproducibility of Results , Time FactorsABSTRACT
PURPOSE: To evaluate the effects of copaiba oil on jaw defects repair in Wistar rats treated with bioglass or adipose tissue. METHODS: A jaw defect was randomly created in forty-two rats and filled with bioglass or adipose tissue. The two groups (Gbio and Gcell) were subdivided in three subgroups with seven animals each according to gavage administration: control (distillated water), oil (copaiba oil) and melox (meloxicam). Euthanasia was performed after forty post-operative days. The bone formation was analyzed regarding the histological aspects. RESULTS: The osteoclasts activity was observed only in four subgroups (p=0.78). Regarding the osteoblasts presence, it was very similar between the subgroups, the difference was due to Gcell-melox (p=0.009) that presented less osteoblastic activity. The inflammatory cells were more evident in Gcell-melox subgroup, however, there was no difference in comparison with the other subgroups (p=0.52). Bone formation was observed in all subgroups, just two animals showed no bone formation even after 40 days. More than 50% of bone matrix mineralization was observed in 56% (23 animals) of the analyzed areas. The bone matrix mineralization was not different between subgroups (p=0.60). CONCLUSIONS: The subgroups that received copaiba oil showed bone repair, although not statistically significant in comparison to subgroups treated whit meloxicam or controls. Copaiba oil administered by gavage had no effect on bone repair in this experimental model. .
Subject(s)
Animals , Male , Bone Regeneration/drug effects , Fabaceae/chemistry , Jaw/drug effects , Osteogenesis/drug effects , Plant Oils/pharmacology , Adipose Tissue/transplantation , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Bone Substitutes/therapeutic use , Ceramics/therapeutic use , Disease Models, Animal , Jaw Abnormalities/drug therapy , Jaw Abnormalities/physiopathology , Jaw/physiopathology , Osteoblasts/drug effects , Osteoblasts/physiology , Osteoclasts/drug effects , Osteoclasts/physiology , Rats, Wistar , Reproducibility of Results , Time Factors , Treatment Outcome , Thiazines/pharmacology , Thiazoles/pharmacology , Wound Healing/drug effectsABSTRACT
Gestational trophoblastic neoplasia (GTN) is the term to describe a set of malignant placental diseases, including invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Both invasive mole and choriocarcinoma respond well to chemotherapy, and cure rates are greater than 90%. Since the advent of chemotherapy, low-risk GTN has been treated with a single agent, usually methotrexate or actinomycin D. Cases of high-risk GTN, however, should be treated with multiagent chemotherapy, and the regimen usually selected is EMA-CO, which combines etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine. This study reviews the literature about GTN to discuss current knowledge about its diagnosis and treatment.
Neoplasia trofoblástica gestacional (NTG) é o termo que descreve o conjunto de anomalias malignas da placenta, incluindo a mola invasora, coriocarcinoma, tumor trofoblástico do sítio placentário e tumor trofoblástico epitelióide. Ambos a mola invasora e o coriocarcinoma respondem bem à quimioterapia, com taxas de cura superiores a 90%. Desde o advento da quimioterapia, NTG de baixo risco tem sido tratada com monoquimioterapia, pelo geral methotrexate ou actinomicina-D. Casos de NTG de alto risco, contudo, devem ser tratados com poliquimioterapia, e o regime usualmente escolhido é o EMA-CO que combina etoposide, methotrexate, actinomicina-D, ciclofosfamida e vincristina. Esse estudo revê a literatura sobre NTG a fim de discutir os conhecimentos atuais sobre seu diagnóstico e tratamento.
Subject(s)
Animals , Male , Rats , Cathepsins/analysis , Cystatins/analysis , Cysteine Proteinase Inhibitors/metabolism , Endopeptidases , Leucine/analogs & derivatives , Osteoclasts/chemistry , Osteoclasts/enzymology , Salivary Proteins and Peptides/analysis , Bone Matrix/chemistry , Bone Matrix/enzymology , Cathepsin L , Cysteine Endopeptidases , Cathepsins/antagonists & inhibitors , Cathepsins/metabolism , Cystatins/metabolism , Cysteine Proteinase Inhibitors/toxicity , Leucine/metabolism , Leucine/toxicity , Lysosomes/enzymology , Microscopy, Immunoelectron , Osteoclasts/drug effects , Osteoclasts/ultrastructure , Rats, Wistar , Salivary CystatinsABSTRACT
BACKGROUND: The Tridax procumbens flavonoids (TPF), are well known for their medicinal properties among local natives. The TPF are traditionally used for dropsy, anaemia, arthritis, gout, asthma, ulcer, piles, and urinary problems. It also used in treating gastric problems, body pain, and rheumatic pains of joints. The TPF have been reported to increase osteogenic functioning in mesenchymal stem cells. However, their effects on osteoclastogenesis remain unclear. The TPF isolated from T. procumbens and investigated the effects of the TPF inhibit on osteoclast differentiation and bone resorption activities using primary osteoclastic cells. Osteoclast formation was assessed by counting the number of tartrate resistant acid phosphatase (TRAP) positive multinucleated cells and by measuring both TRAP activities. RESULTS: The TPF significantly suppressed the RANKL-induced differentiation of osteoclasts and the formation of pits in primary osteoclastic cells. The TPF also decreased the expression of mRNAs related to osteoclast differentiation, including Trap, Cathepsin K, Mmp-9, and Mmp-13 in primary osteoclastic cells. The treatment of primary osteoclastic cells with the TPF decreased Cathepsin K, Mmp-9, and Mmp-13 proteins expression in primary osteoclastic cells. CONCLUSION: These results indicated that TPF inhibit osteoclastogenesis and pits formation activities. Our results suggest that the TPF could be a potential anti-bone resorptic agent to treat patients with bone loss-associated diseases such as osteoporosis.
Subject(s)
Animals , Male , Mice , Osteoclasts/drug effects , Flavonoids/pharmacology , Bone Resorption , Cell Differentiation/drug effects , Asteraceae/chemistry , Flavonoids/isolation & purification , RNA, Messenger , Tartrate-Resistant Acid Phosphatase/drug effects , Mice, Inbred C57BLABSTRACT
Bisphosphonates have been increasingly used not only to treat bone diseases as well as conditions such as osteopenia and osteoporosis, but also in oncotherapy. The use of bisphosphonates induces clinicians to fear and care. These reactions are associated with controversy resulting from lack of in-depth knowledge on the mechanisms of action as well as lack of a more accurate assessment of side effects. Scientific and clinical knowledge disclosure greatly contributes to professionals' discernment and inner balance, especially orthodontists. Fear does not lead to awareness. For these reasons, we present an article that focuses on that matter. This article was adapted from different journals of different dental specialties, as mentioned on footnote. There is no scientific evidence demonstrating that bisphosphonates are directly involved with etiopathogenic mechanisms of osteonecrosis and jaw osteomyelitis. Their use is contraindicated and limited in cases of dental treatment involving bone tissue. Nevertheless, such fact is based on professional opinion, case reports, and personal experience or experiment trials with failing methods. Additional studies will always be necessary; however, in-depth knowledge on bone biology is of paramount importance to offer an opinion about the clinical use of bisphosphonates and their further implications. Based on bone biopathology, this article aims at contributing to lay the groundwork for this matter.
Cada vez mais se usa os bisfosfonatos nos tratamentos de doenças e de estados ósseos, como a osteopenia e osteoporose, assim como nos protocolos oncoterápicos. O uso dos bisfosfonatos induz muitas reações de medo e cuidado, associadas a polêmicas e controvérsias quase sempre resultantes de uma falta de conhecimento mais profundo dos mecanismos de ação e da falta de uma avaliação mais criteriosa de seus efeitos colaterais. A divulgação e o conhecimento dos aspectos científicos e clínicos contribuem, em muito, para o discernimento e tranquilidade dos profissionais, especialmente dos ortodontistas. O medo não resulta em conscientização. Por essas razões, apresentamos alguns artigos sobre o mesmo assunto, semelhantes e adaptados, em revistas voltadas para as diferentes especialidades odontológicas, entre os quais o citado na nota de rodapé. Nos mecanismos etiopatogênicos da osteonecrose e nas osteomielites, nos maxilares, os bisfosfonatos não se encaixam como um dos fatores diretamente envolvidos e com base em evidências científicas. Suas contraindicações e limitações na prática odontológica como fator limitante de alguns tratamentos envolvendo o tecido ósseo estão baseadas, principalmente, em opiniões, casos clínicos e na experiência pessoal ou trabalhos experimentais com algumas falhas nos métodos experimentais. Sempre serão necessários mais estudos, mas um cuidado importante é se aprofundar no conhecimento da biologia óssea para, quando necessário, emitir-se opiniões sobre protocolos de conduta na clínica odontológica quanto ao uso bisfosfonatos e suas implicações. Esse artigo objetiva contribuir na fundamentação de abordagens sobre esse assunto a partir da biopatologia óssea.
Subject(s)
Humans , Bone Density Conservation Agents/therapeutic use , Diphosphonates/therapeutic use , Orthodontics, Corrective , Apoptosis/drug effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bone Density Conservation Agents/adverse effects , Bone Density/drug effects , Bone Diseases, Metabolic/drug therapy , Bone Remodeling/drug effects , Bone and Bones/drug effects , Diphosphonates/adverse effects , Evidence-Based Dentistry , Jaw Diseases/chemically induced , Neoadjuvant Therapy , Neoplasms/therapy , Orthodontics, Corrective , Osteoclasts/drug effects , Osteomyelitis/chemically induced , Osteoporosis/drug therapyABSTRACT
Introduction: Nicotine is harmful to angiogenesis, osteogenesis and synthesis of collagen. Objective: The aim of this study was to investigate the effect of nicotine on bone remodeling during orthodontic movement in rats. Methods: Eighty male Wistar rats were randomly divided into three groups: Group C (control), group CM (with orthodontic movement) and group NM (nicotine with orthodontic movement) groups. The animals comprising groups C and CM received 0.9% saline solution while group NM received nicotine solution (2 mg/kg). A nickel-titanium closed-coil spring was used to induce tooth movement. The animals were euthanized and tissue specimens were processed histologically. We quantified blood vessels, Howship's lacunae and osteoclast-like cells present in the tension and compression areas of periodontal ligaments. The extent of bone formation was evaluated under polarized light to determine the percentage of immature/mature collagen. Results: We observed lower blood vessel densities in the NM group in comparison to the CM group, three (p < 0.001) and seven (p < 0.05) days after force application. Osteoclast-like cells and Howship's lacunae in the NM group presented lower levels of expression in comparison to the CM group, with significant differences on day 7 (p < 0.05 for both variables) and day 14 (p < 0.05 for osteoclast-like cells and p < 0.01 for Howship's lacunae). The percentage of immature collagen increased in the NM group in comparison to the CM group with a statistically significant difference on day 3 (p < 0.05), day 7 (p < 0.001), day 14 (p < 0.001) and day 21 (p < 0.001). Conclusions: Nicotine affects bone remodeling during orthodontic movement, reducing angiogenesis, osteoclast-like cells and Howship's lacunae, thereby delaying the collagen maturation process in developed bone matrix. .
Introdução: a nicotina apresenta efeito prejudicial sobre a angiogênese, osteogênese e síntese de colágeno. Objetivo: investigar a ação da nicotina sobre a remodelação óssea durante o movimento dentário induzido em ratos. Métodos: oitenta ratos machos Wistar foram divididos em três grupos: grupo C (sem indução de movimento dentário e sem a ação da nicotina - controle); grupo CM (indução de movimento dentário) e grupo NM (indução de movimento dentário associado à ação da nicotina). Os animais dos grupos C e CM receberam solução salina a 0,9% e os animais do grupo NM receberam nicotina (solução PA a 98% diluída em solução salina a 0,9% estéril) por via subcutânea (2mg/kg). Após a eutanásia dos animais, com 3, 7, 14 e 21 dias de uso da mola ortodôntica, os espécimes teciduais foram processados histologicamente e quantificou-se o número de vasos sanguíneos, lacunas de Howship e células osteoclásticas nos lados de tração e compressão do ligamento periodontal. A neoformação óssea foi avaliada por meio de luz polarizada, para determinar a porcentagem de colágeno maduro e imaturo. Resultados: observou-se que a quantidade de vasos sanguíneos diminuiu no grupo NM, quando comparado ao grupo CM, nos períodos de três (p < 0,001) e sete (p < 0,05) dias. Quanto às células osteoclásticas e lacunas de Howship, o grupo NM apresentou menores níveis de expressão em relação ao grupo CM, com diferença estatisticamente significativa nos períodos de 7 e 14 dias. A porcentagem de colágeno imaturo apresentou-se aumentada no grupo NM, quando comparado ao grupo CM, em todos os períodos analisados, com diferença e...
Subject(s)
Animals , Male , Rats , Alveolar Process/drug effects , Bone Remodeling/drug effects , Nicotine/pharmacology , Periodontal Ligament/drug effects , Tooth Movement Techniques , Alveolar Process/blood supply , Bone Resorption/pathology , Collagen/drug effects , Dental Alloys/chemistry , Dental Cementum/blood supply , Dental Cementum/drug effects , Molar/blood supply , Molar/drug effects , Neovascularization, Physiologic/drug effects , Nickel/chemistry , Orthodontic Wires , Osteoclasts/drug effects , Osteogenesis/drug effects , Periodontal Ligament/blood supply , Random Allocation , Rats, Wistar , Stress, Mechanical , Time Factors , Titanium/chemistry , Tooth Movement Techniques/instrumentation , Tooth Root/blood supply , Tooth Root/drug effectsABSTRACT
PURPOSE: To analyze the effects of aqueous ozone irrigation over bone healing in hyperglycemia-induced rats. METHODS: Forty-eight male Wistar rats were allocated into Group H (hyperglycemic) or Group N (control). Monocortical bone wound were performed on femurs' anterolateral face. Wounds were treated with a trans-operatory single irrigation of 100ml of aqueous ozone [0.004mg/ml] whereas control groups received 100ml of pure water (Milli-Q®). Histomorphological and histomorphometrical analyses were accomplished after seven, 14 and 21 days. Kruskal-Wallis and Mann-Whitney statistical tests were applied for bone neoformation quantification and assessment. RESULTS: Aqueous ozone wounds irrigated revealed diffuse hemorrhage and increased neoformed of blood vessels number. There was no statistical significant difference in bone trabeculae neoformation. After seven and 14 days, the number of osteoclasts was higher in aqueous ozone groups than in those treated with pure water. CONCLUSION: Independently of blood glucose levels, aqueous ozone allowed an increase in blood vessels neoformation and osteoclast migration, without affect bone trabeculae neoformation.
Subject(s)
Animals , Male , Rats , Bone Regeneration/drug effects , Hyperglycemia/physiopathology , Ozone/therapeutic use , Wound Healing/drug effects , Blood Glucose/drug effects , Osteoclasts/cytology , Osteoclasts/drug effects , Random Allocation , Rats, Wistar , Reference Values , Time Factors , Therapeutic Irrigation/methods , Wound Healing/physiologyABSTRACT
OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 is an inhibitory receptor primarily expressed by immune cells. This study was undertaken to define the role of this molecule in osteoclast differentiation and rheumatoid arthritis. METHODS: In vitro osteoclast assays were performed to characterize the role of Leukocyte-associated immunoglobulin-like receptor-1 in murine and human osteoclastogenesis. Human Leukocyte-associated immunoglobulin-like receptor-1 expression was assessed by immunohistochemistry staining in the synovium of patients with rheumatoid arthritis. The levels of soluble Human Leukocyte-associated immunoglobulin-like receptor-1 were determined by enzyme-linked immunosorbent assay. RESULTS: We found that multinucleated osteoclast formation from mouse bone marrow cells was inhibited by treatment with a monoclonal antibody against mouse Leukocyte-associated immunoglobulin-like receptor-1 in vitro. By immunohistochemistry, we found that Leukocyte-associated immunoglobulin-like receptor-1 was mainly expressed by macrophages in the inflamed synovial tissue of rheumatoid arthritis patients. In addition, serum and synovial fluid levels of soluble Leukocyte-associated immunoglobulin-like receptor-1 were higher in rheumatoid arthritis patients compared to healthy controls or osteoarthritis patients. Moreover, overexpression of Leukocyte-associated immunoglobulin-like receptor-1 in CD14+ monocytes from healthy volunteers also inhibited human osteoclastogenesis. CONCLUSION: Collectively, these data demonstrate for the first time that Leukocyte-associated immunoglobulin-like receptor-1 inhibits osteoclastogenesis. Therefore, these results may have therapeutic implications for the treatment of rheumatoid arthritis. .
Subject(s)
Adult , Aged , Animals , Female , Humans , Male , Mice , Middle Aged , Arthritis, Rheumatoid/metabolism , Osteoclasts/cytology , Receptors, Immunologic/physiology , /blood , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Bone Marrow Cells/pathology , Cell Differentiation/physiology , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunohistochemistry , Osteoclasts/drug effects , Osteoprotegerin/physiology , RANK Ligand/blood , Receptors, Immunologic/analysis , Receptors, Immunologic/antagonists & inhibitors , Synovial Membrane/metabolismABSTRACT
Osteoporosis is a chronic disease characterized by a decrease in bone mineral density [BMD] and corruption of the microarchitectural structure of bone tissue. It was investigated whether methylprednisolone had a favorable effect on osteoporotic bone tissue in Oophorectomy induced osteoporotic rats whose endogenous adrenaline levels are suppressed with metyrosine. Bone Mineral Density, number of osteoblast-osteoclast, bone osteocalcin levels and alkaline phosphatase [ALP] measurements were performed. Obtained results were compared with that of alendronate. Oophorectomy induced osteoporosis was exacerbated by methylprednisolone. Alentronate prevented ovariectomised induced osteoporosis, but it couldn't prevent methylprednisolone +ovariectomised induced osteoporosis in rats. Combined treatment with methylprednisolon and metyrosine was the best treatment for preventing osteoporosis but metyrosine alone couldn't prevent osteoporosis in ovariectomised rats
Subject(s)
Female , Animals, Laboratory , Methyltyrosines , Rats , Osteoclasts/drug effects , Prednisolone , Prednisolone/adverse effects , Drug Combinations , Ovariectomy/adverse effects , Osteoblasts/drug effects , Bone Density/drug effects , Methylprednisolone/adverse effects , Methylprednisolone , Osteocalcin/drug effects , Alkaline Phosphatase , Alendronate , Treatment OutcomeABSTRACT
Platinum nanoparticles (PtNP) exhibit remarkable antioxidant activity. There is growing evidence concerning a positive relationship between oxidative stress and bone loss, suggesting that PtNP could protect against bone loss by modulating oxidative stress. Intragastric administration of PtNP reduced ovariectomy (OVX)-induced bone loss with a decreased level of activity and number of osteoclast (OC) in vivo. PtNP inhibited OC formation by impairing the receptor activator of nuclear factor-kappaB ligand (RANKL) signaling. This impairment was due to a decreased activation of nuclear factor-kappaB and a reduced level of nuclear factor in activated T-cells, cytoplasmic 1 (NFAT2). PtNP lowered RANKL-induced long lasting reactive oxygen species as well as intracellular concentrations of Ca2+ oscillation. Our data clearly highlight the potential of PtNP for the amelioration of bone loss after estrogen deficiency by attenuated OC formation.