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1.
Actual. osteol ; 16(2): 140-153, mayo.-ago. 2020. ilus, graf
Article in Spanish | LILACS | ID: biblio-1129814

ABSTRACT

La osteoporosis y las enfermedades cardiovasculares son patologías prevalentes en mujeres posmenopáusicas. La calcificación vascular es un proceso en el que se produce una distorsión de la arquitectura natural del tejido arterial con una transformación símil osteogénica. La fisiología vascular y la osteogénesis (formación y remodelación ósea) comparten una complejidad metabólica y funcional crítica, que ha sido poco explorada en forma conjunta, lo que ha impulsado la concepción del Eje Óseo-Vascular como nueva área de investigación, con una visión de estudio integradora con la finalidad de identificar vínculos entre ambos sistemas. En virtud de la controversia planteada sobre los riesgos/beneficios de la terapia de reemplazo hormonal para prevenir enfermedades asociadas a la menopausia, se ha incentivado la búsqueda de nuevas opciones de tratamiento. Los fitoestrógenos, como compuestos nutracéuticos, surgen como una potencial alternativa terapéutica. En particular, las isoflavonas presentan gran analogía estructural con el estrógeno humano 17ß-estradiol, lo que les permite unirse al receptor de estrógenos e inducir acciones estrogénicas tanto en células animales como humanas. Basado en la experiencia propia como en lo reportado en la bibliografía, este artículo analiza la información disponible sobre las acciones vasculares y óseas de los fitoestrógenos (específicamente la isoflavona genisteína), con una visión de ciencia traslacional. Es de esperar que los avances en el conocimiento derivado de la ciencia básica, en un futuro cercano, pueda contribuir a decisiones clínicas a favor de promover terapias naturales de potencial acción dual, para la prevención de enfermedades de alta prevalencia y significativo costo social y económico para la población. (AU)


Osteoporosis and cardiovascular diseases are prevalent diseases in postmenopausal women. Vascular calcification is a cellmediated process that leads to the loss of the natural architecture of the arterial vessels due to osteogenic transdifferentiation of smooth muscle cells, and matrix mineralization. Vascular physiology and osteogenesis (bone formation and remodeling) share a critical metabolic and functional complexity. Given the emerging integrative nature of the bonevascular axis, links between both systems are a matter of ongoing interest. In view of the controversy stated about the risks/benefits of hormone replacement therapy to prevent diseases associated with menopause, phytoestrogens arise as a potential natural therapeutic alternative. In particular, isoflavones have a strong structural analogy with the human estrogen 17ß-estradiol, that allows them to bind to the estrogen receptor and induce estrogenic actions in animal and human cells. Based in on our own experience and the information available in the literature, in this paper we provide an overview of the role of phytoestrogens on vascular and bone tissues, with focus on Genistein actions. We wish that the basic knowledge acquired may contribute to guide clinical decisions for the promotion of natural therapies for the treatment of diseases that conspire against human health. (AU)


Subject(s)
Humans , Male , Female , Osteogenesis/drug effects , Phytoestrogens/therapeutic use , Atherosclerosis/drug therapy , Vascular Calcification/drug therapy , Osteogenesis/physiology , Menopause , Cardiovascular Diseases/complications , Osteoporosis, Postmenopausal , Bone Remodeling , Genistein/therapeutic use , Phytoestrogens/classification , Phytoestrogens/pharmacology , Atherosclerosis/physiopathology , Estrogens/biosynthesis , Vascular Calcification/physiopathology , Vascular Calcification/metabolism
2.
Braz. oral res. (Online) ; 34: e007, 2020. graf
Article in English | LILACS | ID: biblio-1055531

ABSTRACT

Abstract The aim of this study was to assess the influence of cyclosporine administration on the repair of critical-sized calvaria defects (CSDs) in rat calvaria filled with diverse biomaterials. Sixty animals were divided into two groups: the control (CTR) group (saline solution) and the cyclosporine (CCP) group (cyclosporine, 10 mg/kg/day). These medications were administered daily by gavage, beginning 15 days before the surgical procedure and lasting until the day the animals were euthanized. A CSD (5 mm Ø) was made in the calvaria of each animal, which was allocated to one of 3 subgroups, according to the biomaterial used to fill the defect: coagulum (COA), deproteinized bovine bone (DBB), or biphasic calcium phosphate ceramics of hydroxyapatite and β-phosphate tricalcium (HA/TCP). Euthanasia of the animals was performed 15 and 60 days after the surgical procedure (n = 5 animals/period/subgroup). Bone repair (formation) assessment was performed through microtomography and histometry, while the analyses of the expression of the BMP2, Osteocalcin, and TGFβ1 proteins were performed using immunohistochemistry. The CSDs not filled with biomaterials demonstrated lower bone formation in the CCP group. At 15 days, less bone formation was observed in the CSDs filled with DBB, a smaller volume of mineralized tissue was observed in the CSDs filled with HA/TCP, and the expression levels of BMP2 and osteocalcin were lower in the CCP group compared to the CTR group. The use of cyclosporine impaired bone repair in CSD, and this effect can be partially explained by the suppression of BMP2 and osteocalcin expression.


Subject(s)
Animals , Male , Rats , Osteogenesis/drug effects , Bone Regeneration/drug effects , Cyclosporine/pharmacology , Bone Substitutes/pharmacology , Calcineurin Inhibitors/pharmacology , Skull/drug effects , Skull/pathology , Time Factors , Immunohistochemistry , Random Allocation , Osteocalcin/analysis , Reproducibility of Results , Transforming Growth Factor beta1/analysis , Bone Morphogenetic Protein 2/analysis , X-Ray Microtomography
3.
Braz. oral res. (Online) ; 34: e007, 2020. graf
Article in English | LILACS | ID: biblio-1089397

ABSTRACT

Abstract The aim of this study was to assess the influence of cyclosporine administration on the repair of critical-sized calvaria defects (CSDs) in rat calvaria filled with diverse biomaterials. Sixty animals were divided into two groups: the control (CTR) group (saline solution) and the cyclosporine (CCP) group (cyclosporine, 10 mg/kg/day). These medications were administered daily by gavage, beginning 15 days before the surgical procedure and lasting until the day the animals were euthanized. A CSD (5 mm Ø) was made in the calvaria of each animal, which was allocated to one of 3 subgroups, according to the biomaterial used to fill the defect: coagulum (COA), deproteinized bovine bone (DBB), or biphasic calcium phosphate ceramics of hydroxyapatite and β-phosphate tricalcium (HA/TCP). Euthanasia of the animals was performed 15 and 60 days after the surgical procedure (n = 5 animals/period/subgroup). Bone repair (formation) assessment was performed through microtomography and histometry, while the analyses of the expression of the BMP2, Osteocalcin, and TGFβ1 proteins were performed using immunohistochemistry. The CSDs not filled with biomaterials demonstrated lower bone formation in the CCP group. At 15 days, less bone formation was observed in the CSDs filled with DBB, a smaller volume of mineralized tissue was observed in the CSDs filled with HA/TCP, and the expression levels of BMP2 and osteocalcin were lower in the CCP group compared to the CTR group. The use of cyclosporine impaired bone repair in CSD, and this effect can be partially explained by the suppression of BMP2 and osteocalcin expression.


Subject(s)
Animals , Male , Rats , Osteogenesis/drug effects , Bone Regeneration/drug effects , Cyclosporine/pharmacology , Bone Substitutes/pharmacology , Calcineurin Inhibitors/pharmacology , Skull/drug effects , Skull/pathology , Time Factors , Immunohistochemistry , Random Allocation , Osteocalcin/analysis , Reproducibility of Results , Transforming Growth Factor beta1/analysis , Bone Morphogenetic Protein 2/analysis , X-Ray Microtomography
4.
J. pediatr. (Rio J.) ; 95(5): 567-574, Sept.-Oct. 2019. tab
Article in English | LILACS | ID: biblio-1040356

ABSTRACT

Abstract Objective: The objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. Methods: This was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n = 42) (20 µg EE/150 µg desogestrel), oral contraceptives 2 (n = 66) (30 µg EE/3 mg drospirenone), and a control group (n = 70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. Results: At study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. Conclusion: Adolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.


Resumo: Objetivo: O objetivo deste estudo foi avaliar os efeitos de dois contraceptivos orais combinados de baixa dosagem por um ano sobre o metabolismo ósseo em adolescentes. Métodos: Este foi um estudo quase experimental. As adolescentes foram divididas em três grupos: contraceptivos orais 1 (n = 42) (20 µg de EE/150 µg de desogestrel), contraceptivos orais 2 (n = 66) (30 µg EE/3 mg de drospirenona) e grupo controle (n = 70). As adolescentes foram submetidas à avaliação antropométrica e densitometria (raio-X de dupla energia). Foram avaliados a idade óssea e os marcadores de formação óssea (osteocalcina e fosfatase alcalina óssea). As usuárias de contraceptivos orais foram novamente avaliadas após 12 meses. A análise de regressão linear foi utilizada para estudar, indiretamente, o efeito de cada ano adicional da idade cronológica sobre as variáveis antropométricas e densitométricas e sobre os marcadores ósseos no grupo de controle. Resultados: No início do estudo, não foram observadas diferenças significativas nas variáveis analisadas entre as usuárias de contraceptivos orais 1, contraceptivos orais 2 e o grupo controle. A análise de regressão linear mostrou um aumento na densidade mineral óssea e no conteúdo mineral ósseo para cada ano adicional. Houve uma redução significativa nos níveis de fosfatase alcalina óssea e não foi observada diferença significativa para osteocalcina nos indivíduos controles. A comparação das variáveis do raio-X de dupla energia no início e após um ano não mostrou diferença significativa no grupo de contraceptivos orais 1 ou contraceptivos orais 2. Foi observada uma redução significativa nos níveis de fosfatase alcalina óssea e osteocalcina nos dois grupos contraceptivos orais 1 e contraceptivos orais 2. Conclusão: As adolescentes atingiram o pico de massa óssea durante essa fase da vida. Duas formulações de contraceptivos hormonais orais de baixa dosagem, após um ano de uso, se associaram a menor incremento na densidade mineral óssea e menor concentração de marcadores de formação óssea quando confrontados com resultados de adolescentes não usuárias de contraceptivos.


Subject(s)
Humans , Female , Child , Adolescent , Young Adult , Osteogenesis/drug effects , Bone Density/drug effects , Desogestrel/administration & dosage , Contraceptives, Oral, Hormonal/administration & dosage , Ethinyl Estradiol/administration & dosage , Androstenes/administration & dosage , Osteogenesis/physiology , Reference Values , Time Factors , Bone Density/physiology , Linear Models , Osteocalcin/analysis , Anthropometry , Analysis of Variance , Statistics, Nonparametric , Alkaline Phosphatase/analysis , Non-Randomized Controlled Trials as Topic
5.
Braz. oral res. (Online) ; 33: e079, 2019. graf
Article in English | LILACS | ID: biblio-1019604

ABSTRACT

Abstract Cell therapy associated with guided bone regeneration (GBR) can be used to treat bone defects under challenging conditions such as osteoporosis. This study aimed to evaluate the effect of mesenchymal stem cells (MSCs) in combination with a poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT) membrane on bone repair in osteoporotic rats. Osteoporosis was induced in female rats by bilateral removal of the ovaries (OVX) or sham surgery (SHAM), and the osteoporotic condition was characterized after 5 months by microtomographic and morphometric analyses. Calvarial defects were created in osteoporotic rats that immediately received the PVDF-TrFE/BT membrane. After 2 weeks, bone marrow-derived MSCs from healthy rats, characterized by the expression of surface markers using flow cytometry, or phosphate-buffered saline (PBS) (Control) were injected into the defects and bone formation was evaluated 4 weeks post-injection by microtomographic, morphometric, and histological analyses. A reduction in the amount of bone tissue in the femurs of OVX compared with SHAM rats confirmed the osteoporotic condition of the experimental model. More bone formation was observed when the defects were injected with MSCs compared to that with PBS. The modification that we are proposing in this study for the classical GBR approach where cells are locally injected after a membrane implantation may be a promising therapeutic strategy to increase bone formation under osteoporotic condition.


Subject(s)
Animals , Female , Polyvinyls/pharmacology , Titanium/pharmacology , Barium Compounds/pharmacology , Guided Tissue Regeneration/methods , Mesenchymal Stem Cells/physiology , Osteogenesis/drug effects , Osteoporosis/physiopathology , Osteoporosis/therapy , Polyvinyls/chemistry , Time Factors , Titanium/chemistry , Bone Regeneration/drug effects , Bone Regeneration/physiology , Ovariectomy , Random Allocation , Bone Density , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Barium Compounds/chemistry , Imaging, Three-Dimensional , Mesenchymal Stem Cells/chemistry , Flow Cytometry
6.
J. appl. oral sci ; 27: e20180641, 2019. tab, graf
Article in English | LILACS, BBO | ID: biblio-1012519

ABSTRACT

Abstract Objectives: Infection, inflammation and bone resorption are closely related events in apical periodontitis development. Therefore, we sought to investigate the role of cyclooxygenase (COX) in osteoclastogenesis and bone metabolism signaling in periapical bone tissue after bacterial lipopolysaccharide (LPS) inoculation into root canals. Methodology: Seventy two C57BL/6 mice had the root canals of the first molars inoculated with a solution containing LPS from E. coli (1.0 mg/mL) and received selective (celecoxib) or non-selective (indomethacin) COX-2 inhibitor. After 7, 14, 21 and 28 days the animals were euthanized and the tissues removed for total RNA extraction. Evaluation of gene expression was performed by qRT-PCR. Statistical analysis was performed using analysis of variance (ANOVA) followed by post-tests (α=0.05). Results: LPS induced expression of mRNA for COX-2 (Ptgs2) and PGE2 receptors (Ptger1, Ptger3 and Ptger4), indicating that cyclooxygenase is involved in periapical response to LPS. A signaling that favours bone resorption was observed because Tnfsf11 (RANKL), Vegfa, Ctsk, Mmp9, Cd36, Icam, Vcam1, Nfkb1 and Sox9 were upregulated in response to LPS. Indomethacin and celecoxib differentially modulated expression of osteoclastogenic and other bone metabolism genes: celecoxib downregulated Igf1r, Ctsk, Mmp9, Cd36, Icam1, Nfkb1, Smad3, Sox9, Csf3, Vcam1 and Itga3 whereas indomethacin inhibited Tgfbr1, Igf1r, Ctsk, Mmp9, Sox9, Cd36 and Icam1. Conclusions: We demonstrated that gene expression for COX-2 and PGE2 receptors was upregulated after LPS inoculation into the root canals. Additionally, early administration of indomethacin and celecoxib (NSAIDs) inhibited osteoclastogenic signaling. The relevance of the cyclooxygenase pathway in apical periodontitis was shown by a wide modulation in the expression of genes involved in both bone catabolism and anabolism.


Subject(s)
Animals , Male , Osteogenesis/physiology , Periapical Tissue/drug effects , Periapical Tissue/metabolism , Lipopolysaccharides/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Prostaglandin-Endoperoxide Synthases/physiology , Dental Pulp Cavity/metabolism , Osteogenesis/drug effects , Time Factors , Bone Resorption/metabolism , Gene Expression , Up-Regulation , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Indomethacin/pharmacology , Lipopolysaccharides/analysis , Prostaglandin-Endoperoxide Synthases/analysis , Prostaglandin-Endoperoxide Synthases/drug effects , Receptors, Prostaglandin E/analysis , Reverse Transcriptase Polymerase Chain Reaction , Escherichia coli/metabolism , Cyclooxygenase 2/analysis , Celecoxib/pharmacology , Mice, Inbred C57BL
7.
J. appl. oral sci ; 27: e20180103, 2019. graf
Article in English | LILACS, BBO | ID: biblio-1002400

ABSTRACT

Abstract Objective This study aimed to evaluate the inflammatory effect and bone formation in sterile surgical failures after implantation of a collagen sponge with mesenchymal stem cells from human dental pulp (hDPSCs) and Aloe vera. Material and Methods Rattus norvegicus (n=75) were divided into five experimental groups according to treatment: G1) control (blood clot); G2) Hemospon®; G3) Hemospon® in a culture medium enriched with 8% Aloe vera; G4) Hemospon® in a culture medium containing hDPSCs and G5) Hemospon® in a culture medium enriched with 8% Aloe vera and hDPSCs. On days 7, 15 and 30, the animals were euthanized, and the tibia was dissected for histological, immunohistochemistry and immunofluorescence analyses. The results were analyzed using nonparametric Kruskal-Wallis test and Dunn's post-test. Results On days 7 and 15, the groups with Aloe vera had less average acute inflammatory infiltrate compared to the control group and the group with Hemospon® (p<0.05). No statistically significant difference was found between the groups regarding bone formation at the three experimental points in time. Osteopontin expression corroborated the intensity of bone formation. Fluorescence microscopy revealed positive labeling with Q-Tracker® in hDPSCs before transplantation and tissue repair. Conclusion The results suggest that the combination of Hemospon®, Aloe vera and hDPSCs is a form of clinical treatment for the repair of non-critical bone defects that reduces the inflammatory cascade's effects.


Subject(s)
Humans , Animals , Male , Rats , Bone Regeneration/drug effects , Bone Regeneration/physiology , Plant Extracts/pharmacology , Dental Pulp/cytology , Mesenchymal Stem Cell Transplantation/methods , Aloe/chemistry , Osteogenesis/drug effects , Osteogenesis/physiology , Tibia/drug effects , Tibia/physiology , Tibia/pathology , Time Factors , Immunohistochemistry , Hemostatics/pharmacology , Cell Survival/drug effects , Cell Survival/physiology , Cells, Cultured , Reproducibility of Results , Collagen/pharmacology , Treatment Outcome , Osteopontin/analysis , Flow Cytometry , Microscopy, Fluorescence
8.
J. appl. oral sci ; 27: e20180317, 2019. tab, graf
Article in English | LILACS, BBO | ID: biblio-984571

ABSTRACT

Abstract Bone morphogenetic protein type 2 (BMP-2) and retinoic acid (RA) are osteoinductive factors that stimulate endogenous mechanisms of bone repair which can be applied on management of osseous defects in oral and maxillofacial fields. Objective Considering the different results of RA on osteogenesis and its possible use to substitute/potency BMP-2 effects, this study evaluated the outcomes of BMP-2, RA, and BMP-2+RA treatments on in vitro osteogenic differentiation of human adipose-derived stem cells (ASCs) and the signaling pathway(s) involved. Material and Methods ASCs were treated every other day with basic osteogenic medium (OM) alone or supplemented with BMP-2, RA, or BMP-2+RA. Alkaline phosphatase (ALP) activity was determined using the r-nitrophenol method. Extracellular matrix mineralization was evaluated using von Kossa staining and calcium quantification. Expression of osteonectin and osteocalcin mRNA were determined using qPCR. Smad1, Smad4, phosphorylated Smad1/5/8, BMP-4, and BMP-7 proteins expressions were analyzed using western blotting. Signaling pathway was evaluated using the IPA® software. Results RA promoted the highest ALP activity at days 7, 14, 21, and 28, in comparison to BMP-2 and BMP-2+RA. BMP-2+RA best stimulated phosphorylated Smad1/5/8 protein expression at day 7 and Smad4 expression at days 7, 14, 21, and 28. Osteocalcin and osteonectin mRNA expressions were best stimulated by BMP-2+RA at day 7. Matrix mineralization was most improved by BMP-2+RA at days 12 and 32. Additionally, BMP-2+RA promoted the highest BMP signaling pathway activation at days 7 and 14, and demonstrated more activation of differentiation of bone-forming cells than OM alone. Conclusions In summary, RA increased the effect of BMP-2 on osteogenic differentiation of human ASCs.


Subject(s)
Humans , Osteogenesis/drug effects , Tretinoin/pharmacology , Cell Differentiation/drug effects , Bone Morphogenetic Protein 2/drug effects , Mesenchymal Stem Cells/drug effects , Osteoblasts/drug effects , Osteogenesis/physiology , Reference Values , Time Factors , Osteocalcin/analysis , Osteocalcin/drug effects , Osteonectin/analysis , Osteonectin/drug effects , Cell Differentiation/physiology , Cells, Cultured , Blotting, Western , Reproducibility of Results , Analysis of Variance , Alkaline Phosphatase/analysis , Alkaline Phosphatase/adverse effects , Bone Morphogenetic Protein 2/metabolism , Mesenchymal Stem Cells/metabolism
9.
J. appl. oral sci ; 27: e20180014, 2019. graf
Article in English | LILACS, BBO | ID: biblio-975888

ABSTRACT

Abstract Stanozolol (ST) is a synthetic androgen with high anabolic potential. Although it is known that androgens play a positive role in bone metabolism, ST action on bone cells has not been sufficiently tested to support its clinical use for bone augmentation procedures. Objective: This study aimed to assess the effects of ST on osteogenic activity and gene expression in SaOS-2 cells. Material and Methods: SaOS-2 deposition of mineralizing matrix in response to increasing doses of ST (0-1000 nM) was evaluated through Alizarin Red S and Calcein Green staining techniques at 6, 12 and 24 days. Gene expression of runt-related transcription factor 2 (RUNX2), vitamin D receptor (VDR), osteopontin (SPP1) and osteonectin (ON) was analyzed by RT-PCR. Results: ST significantly influenced SaOS-2 osteogenic activity: stainings showed the presence of rounded calcified nodules, which increased both in number and in size over time and depending on ST dose. RT-PCR highlighted ST modulation of genes related to osteogenic differentiation. Conclusions: This study provided encouraging results, showing ST promoted the osteogenic commitment of SaOS-2 cells. Further studies are required to validate these data in primary osteoblasts and to investigate ST molecular pathway of action.


Subject(s)
Humans , Osteogenesis/drug effects , Stanozolol/pharmacology , Gene Expression/drug effects , Anabolic Agents/pharmacology , Osteoblasts/drug effects , Time Factors , Calcification, Physiologic/drug effects , Linear Models , Osteonectin/analysis , Osteonectin/drug effects , Reproducibility of Results , Analysis of Variance , Receptors, Calcitriol/analysis , Receptors, Calcitriol/drug effects , Cell Line, Tumor/drug effects , Core Binding Factor Alpha 1 Subunit/analysis , Core Binding Factor Alpha 1 Subunit/drug effects , Osteopontin/analysis , Osteopontin/drug effects , Real-Time Polymerase Chain Reaction
10.
J. appl. oral sci ; 27: e20180150, 2019. graf
Article in English | LILACS, BBO | ID: biblio-975883

ABSTRACT

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 Phosphatase
11.
Acta cir. bras ; 34(7): e201900704, 2019. tab, graf
Article in English | LILACS | ID: biblio-1038112

ABSTRACT

Abstract Purpose: The effects of resveratrol administration on calvarial bone defects with alloplastic graft material was investigated for osteoinductive reaction and bone development in rats. Methods: Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows: control (defect) group, defect + graft group, and defect + graft + resveratrol group. A calvarial bone defect was created in all groups, alloplastic bone grafts were applied to the defect in the 2nd and 3rd group, resveratrol (5 mg/kg/day) was added to the drinking water of the animals following graft application for 28 days in the 3rd group. Results: Increase in osteoclasts and necrotic changes were observed histopathologically in the control group. In the 2nd group, reduction of inflammation, congestion of blood vessels, increased osteblastic activity, osteoinductive effect, progression of osteocyte development and increased collagen fibers in connective tissue were observed. In the 3rd group, osteoblasts seemed to secrete bone matrix and accelerate osteoinductive effect with increased osteopregenitor activity and positive osteopontin and osteonectin expressions. Conclusion: Resveratrol treatment was thought to be an alternative and supportive drug for implant application by inducing new bone formation in the calvaral defect region as a result of short-term treatment.


Subject(s)
Animals , Male , Rats , Skull/surgery , Bone Regeneration/drug effects , Bone Transplantation/methods , Bone Substitutes/administration & dosage , Resveratrol/administration & dosage , Osteoblasts/drug effects , Osteogenesis/drug effects , Skull/drug effects , Drug Administration Schedule , Osteonectin/administration & dosage , Osseointegration/drug effects , Bone Substitutes/therapeutic use , Disease Models, Animal , Osteopontin/administration & dosage
12.
Acta cir. bras ; 34(3): e201900306, 2019. tab, graf
Article in English | LILACS | ID: biblio-989063

ABSTRACT

Abstract Purpose: To investigate the effects of allopurinol administration on osteoinductive reaction and bone development with graft material. Methods: Thirty-six Wistar albino rats were divided into 3 groups. In the control group, calvarial bone defect was only created without any treatment. In the Defect + Graft group, allograft treatment was performed by forming 8 mm calvarial bone defect. In the Defect + Graft + Allopurinol group, alloplastic bone graft was placed in the calvarial bone defect and then, allopurinol (50 mg/kg/day) treatment was intraperitoneally applied for 28 days. Results: Histopathological examination revealed inflammation, congestion in the vessels, and an increase in osteoclast cells in the defect area. We also observed that new osteocyte cells, increase in connective tissue fibers, and new bone trabeculae. Osteopontin expression was positive in osteoblast cells and lacunated osteocyte cells were located in the periphery of the new bone trabeculae. Osteopontin expression was also positive in osteoblasts and osteocytes cells of new bone trabeculae in the graft site. Conclusion: It has been shown that allopurinol treatment in rat calvaria defects may induce osteoblastic activity, matrix development, mature bone cell formation and new bone formation when used with autogenous grafts.


Subject(s)
Animals , Rats , Osteogenesis/drug effects , Skull/drug effects , Wound Healing/drug effects , Bone Regeneration/drug effects , Allopurinol/pharmacology , Skull/injuries , Rats, Wistar , Disease Models, Animal , Autografts
13.
J. appl. oral sci ; 27: e20180574, 2019. graf
Article in English | LILACS, BBO | ID: biblio-1040233

ABSTRACT

Abstract Hypertension is one of the main causes of premature death in the world; also, it is associated with several bone alterations. Preclinical studies have demonstrated delayed alveolar bone healing in hypertensive rats. However, losartan has been favorable for consolidation of bone grafts and reduction in active periodontitis. Therefore, losartan is suggested to be effective in bone formation stages, as well as in the synthesis of matrix proteins and mineralization. Objectives: To evaluate the alveolar bone dynamics in hypertensive rats treated with losartan by laser confocal microscopy and histological analysis. Methodology: Thirty-two rats, 16 spontaneously hypertensive rats (SHR) and 16 Wistar albinus rats, treated or not with losartan (30 mg/kg/day) were used. Calcein fluorochrome at 21 days and alizarin red fluorochrome at 49 days were injected in rats (both 20 mg/kg). The animals were submitted to euthanasia 67 days after treatment, and then the right maxilla was removed for laser confocal microscopy analysis and the left maxilla for histological analysis. Results: This study showed a greater calcium marking in normotensive animals treated with losartan in relation to the other groups. Laser confocal microscopy parameters showed higher values of bone volume formed, mineralized surface, active surface of mineralization and bone formation rate in normotensive animals treated with losartan. However, a smaller mineralized surface was observed in all hypertensive animals. Conclusion: Losartan can improve bone mineralization parameters under normal physiological conditions, but the same anabolic effect does not occur under hypertension.


Subject(s)
Animals , Male , Losartan/pharmacology , Alveolar Process/drug effects , Alveolar Process/physiopathology , Hypertension/physiopathology , Antihypertensive Agents/pharmacology , Osteogenesis/drug effects , Rats, Inbred SHR , Time Factors , Blood Pressure/drug effects , Bone Regeneration/drug effects , Calcification, Physiologic/drug effects , Reproducibility of Results , Rats, Wistar , Microscopy, Confocal , Alveolar Process/pathology , Fluoresceins/analysis
14.
J. appl. oral sci ; 27: e20180693, 2019. graf
Article in English | LILACS, BBO | ID: biblio-1040226

ABSTRACT

ABSTRACT Objectives: To compare the sealing ability and biocompatibility of Biodentine with mineral trioxide aggregate (MTA) when used as root-end filling materials. Methodology: The Cell Counting Kit-8 (CCK-8) assay was used to compare the cytotoxicity of MTA and Biodentine. Twenty-one extracted teeth with a single canal were immersed in an acidic silver nitrate solution after root-end filling. Then, the volume and depth of silver nitrate that infiltrated the apical portion of the teeth were analyzed using micro-computed tomography (micro-CT). Seventy-two roots from 3 female beagle dogs were randomly distributed into 3 groups and apical surgery was performed. After six months, the volume of the bone defect surrounding these roots was analyzed using micro-CT. Results: Based on the results of the CCK-8 assay, MTA and Biodentine did not show statistically significant differences in cytotoxicity (P>0.05). The volume and the depth of the infiltrated nitrate solution were greater in the MTA group than in the Biodentine group (P<0.05). The volume of the bone defect was larger in the MTA group than in the Biodentine group. However, the difference was not significant (P>0.05). The volumes of the bone defects in the MTA and Biodentine groups were smaller than the group without any filling materials (P<0.05). Conclusions: MTA and Biodentine exhibited comparable cellular biocompatibility. Biodentine showed a superior sealing ability to MTA in root-end filling. Both Biodentine and MTA promoted periradicular bone healing in beagle dog periradicular surgery models.


Subject(s)
Humans , Animals , Male , Adolescent , Dogs , Oxides/pharmacology , Periapical Tissue/drug effects , Periodontal Ligament/drug effects , Root Canal Filling Materials/pharmacology , Root Canal Therapy/methods , Wound Healing/drug effects , Silicates/pharmacology , Calcium Compounds/pharmacology , Aluminum Compounds/pharmacology , Osteogenesis/drug effects , Periapical Tissue/cytology , Periapical Tissue/diagnostic imaging , Periodontal Ligament/diagnostic imaging , Time Factors , Tooth Root/surgery , Tooth Root/drug effects , Tooth Root/diagnostic imaging , Bone Regeneration/drug effects , Materials Testing , Cell Count , Cells, Cultured , Reproducibility of Results , Treatment Outcome , Drug Combinations , X-Ray Microtomography
15.
J. appl. oral sci ; 27: e20180621, 2019. graf
Article in English | LILACS, BBO | ID: biblio-1012525

ABSTRACT

Abstract Objective Considering the global public health problem of smoking, which can negatively influence bone tissue repair, the aim of this study is to analyze the influence of photobiomodulation therapy (PBM) on calvaria defects created surgically in specimens under the effect of cigarette smoke and analyzed with use of histomorphometric and immunohistochemistry techniques. Methodology Calvaria defects 4.1 mm in diameter were surgically created in the calvaria of 90-day-old rats (n=60) that were randomly divided into 4 experimental groups containing 15 animals each: control group (C), smoking group (S), laser group (L), and smoke associated with laser group (S+L). The animals were subjected to surgery for calvaria defects and underwent PBM, being evaluated at 21, 45, and 60 days post-surgery. The specimens were then processed for histomorphometric and immunohistochemistry analyses. The area of bone neoformation (ABN), percentage of bone neoformation (PBNF), and the remaining distance between the edges of the defects (D) were analyzed histometrically. Quantitative analysis of the TRAP immunolabeled cells was also performed. The data were subjected to analysis of variance (ANOVA) in conjunction with Tukey's test to verify the statistical differences between groups (p<0.05). Results The smoking group showed less ABN compared to the other experimental groups in all periods, and it also showed more D at 21 days compared to the remaining groups and at 45 days compared to the laser group. The smoking group showed a lower PNBF compared to the laser group in all experimental periods and compared to smoking combined with LLLT group at 21 days. Conclusions PBM acted on bone biomodulation, thus stimulating new bone formation and compensating for the negative factor of smoking, which can be used as a supportive therapy during bone repair processes.


Subject(s)
Animals , Female , Rats , Skull/radiation effects , Wound Healing/radiation effects , Bone Regeneration/drug effects , Low-Level Light Therapy/methods , Cigarette Smoking/physiopathology , Osteogenesis/drug effects , Skull/pathology , Time Factors , Immunohistochemistry , Random Allocation , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Cigarette Smoking/adverse effects
16.
J. oral res. (Impresa) ; 7(8): 350-355, nov. 30, 2018. ilus, tab
Article in English | LILACS | ID: biblio-1121066

ABSTRACT

Introduction: Ostene is a water-soluble wax-like alkylene oxide copolymer preparation for use as a mechanical hemostatic agent. this study aims to evaluate the effects of Ostene on bone healing. materials and methods: twenty albino rabbits were divided into four groups according to post-treatment follow-up (24 hr, 3 days, 7 days, 14 days) with five rabbits in each group. each rabbit in all groups was treated with two study materials (Ostene and Gelfoam). three holes were made in the mandibular bone of each rabbit using 5mm surgical bur; two holes were made on right side: one for testing Ostene and another for Gelfoam. a third hole, on the left side of mandible, was not treated, and was used as a control. finally, the incision was closed. the specimens were collected at different days post-treatment and examined by histopathology. result and discussion: this study showed that there is a significant difference (p-value≤ 0.05) between the Ostene group and the other groups (Gelfoam and control). at 24 hr post intervention, there is a significant difference in osteoblast cell formation (p-value=0.03), and osteoclast cell formation (p-value=0.05). new blood vessel formation, osteoblast and osteoclast cell formation for Ostene group at 3 days post-intervention were also significantly different (p-values = 0.05, 0.03, 0.04, respectively). at 7 days post-intervention p-values were 0.05 for osteoblast formation and 0.04 for osteoclast formation, respectively. after 14 days of healing p-value for osteoblast cell formation in the Ostene group was 0.05 and 0.04 for osteoclast cell formation. conclusions: the bone hemostatic agent Ostene is an effective at enhancing osteogenesis by initiating proliferation of osteoblast and osteoclast cells.


Subject(s)
Animals , Rabbits , Osteogenesis/drug effects , Wound Healing/drug effects , Bone and Bones/drug effects , Hemostatics/pharmacology , Hemostasis , Osteoblasts , Osteoclasts , Disease Models, Animal , Mandible/drug effects
17.
Braz. dent. j ; 29(5): 435-445, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-974183

ABSTRACT

Abstract This study aimed to evaluate the effect of two methods of local application of alendronate and parathyroid hormone (PTH) on bone repair and the systemic implications. A critically sized defect (5 mm) was created in the cranial region of twenty-five male Wistar rats, and the bone removed was particulated, and grafted back to the defect with different treatments. The animals were randomly divided into five groups: A1- bone graft immersion in alendronate solution (3 mg/kg) for 5 minutes; P1- bone graft immersion in PTH solution (20 µg); A2- weekly local applications of alendronate 1 mg/kg; P2- weekly local applications of PTH (20 µg); C- no drugs were used. The animals were euthanized 60 days after surgery. Cranial bone blocks were removed for histological, histomorphometric, and immunohistochemical analyses. MMP-2 and MMP-9 were used for immunolabeling. The kidneys, liver, and brain were also removed from all the rats for histological analysis. The data were submitted for statistical analysis with a level of significance of 0.05 (One-way ANOVA). The group C and group P2 presented a higher quantity of viable bone particles than the remaining groups. Groups A1, A2, and P1 presented with fewer viable bone particles than the control group, with a predominance of non-mineralized connective tissue. The histomorphometric analysis revealed no differences in relative bone area or MMP-2 or MMP-9 immunolabeling between the groups (p>0.05). Group A2 showed presence of fat in the liver consistent with hepatic steatosis. Changes in brain tissue were observed in groups A1 and P1.


Resumo Este estudo visou avaliar o efeito de dois métodos de aplicação local de alendronato e de paratormônio (PTH) no reparo ósseo e avaliar as implicações sistêmicas. Um defeito de tamanho crítico (5 mm) foi criado na calota craniana de vinte e cinco ratos Wistar machos, e o osso removido foi particulado e enxertado de volta no defeito com diferentes tratamentos. Os animais foram divididos aleatoriamente em cinco grupos: A1: imersão do enxerto ósseo em solução de alendronato (3 mg/kg) durante 5 min; P1- imersão do osso em solução de PTH (20 μg); A2- aplicações locais semanais de alendronato 1 mg/kg; P2- aplicações locais semanais de PTH 20 μg; C: não foram utilizados medicamentos. Os animais foram eutanasiados 60 dias após a cirurgia. Foram removidos os blocos ósseos envolvendo a região do defeito para realização das análises histológica, histomorfométrica e imuno-histoquímica. MMP2 e MMP9 foram as imunomarcações utilizadas. Os rins, fígado e cérebro também foram removidos de todos os ratos para análise histológica. Os dados foram submetidos à análise estatística com um nível de significância de 0,05 (One-way ANOVA). A análise histológica revelou que o grupo C e o grupo P2 apresentaram maior quantidade de partículas ósseas viáveis do que as apresentadas pelos demais grupos. Os grupos A1, A2 e P1 apresentaram menos partículas ósseas viáveis em comparação com o grupo controle com predominância de tecido conjuntivo não mineralizado. A análise histomorfométrica não revelou diferenças entres os grupos na área óssea relativa ou em MMP2 e MMP9 (p>0,05). O grupo A2 mostrou presença de gordura no fígado consistente com esteatose hepática. Alterações no tecido cerebral foram observadas nos grupos A1 e P1.


Subject(s)
Animals , Male , Rats , Osteogenesis/drug effects , Parathyroid Hormone/pharmacology , Skull/surgery , Skull/drug effects , Bone Regeneration/drug effects , Alendronate/pharmacology , Wound Healing/drug effects , Bone Resorption , Brain/drug effects , Immunohistochemistry , Bone Transplantation/methods , Alendronate/administration & dosage , Kidney/drug effects , Liver/drug effects
18.
Int. j. morphol ; 36(2): 391-394, jun. 2018. tab, graf
Article in English | LILACS | ID: biblio-954126

ABSTRACT

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 Supplements
19.
Acta cir. bras ; 33(4): 354-361, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-886281

ABSTRACT

Abstract Purpose: To compare bone regeneration in critical-sized defects in rat calvarium using demineralized bone matrix and calcium phosphate cement. Methods: Thirty Wistar rats were divided into 3 groups of 10 animals each. Two defects of 5-mm were made in the parietal bones of each animal. Group I had calcium phosphate cement placed in the experimental defect, Group II had filled with demineralized bone matrix and Group III had with the combination of the matrix and cement in equal parts. All animals had one defect left unfilled to serve as controls. Five animals in each group were sacrificed at 4 and 8 weeks. Histomorphometric analysis was used to quantify the amount of new bone within the defects. Results: The results showed that demineralized bone matrix-treated defects had significantly more new bone at 4 weeks compared to calcium phosphate cement-treated defects (p=0.03) and also had significantly more new bone at 8 weeks compared to unfilled defects (p=0.04). Conclusions: The demineralized bone matrix was superior to calcium phosphate cement in bone regeneration. It seems that calcium phosphate cement acted by inhibiting the osteogenesis when associated with a demineralized bone matrix and this combination should not be recommended.


Subject(s)
Animals , Male , Osteogenesis/drug effects , Bone Cements/pharmacology , Bone Matrix , Bone Regeneration/drug effects , Calcium Phosphates/pharmacology , Bone Substitutes/pharmacology , Osteogenesis/physiology , Skull/drug effects , Skull/physiology , Time Factors , Bone Regeneration/physiology , Materials Testing , Reproducibility of Results , Treatment Outcome , Rats, Wistar
20.
Acta cir. bras ; 33(4): 324-332, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-886287

ABSTRACT

Abstract Purpose: To investigate if the inorganic bovine bone matrix changes the bone formation in rats submitted to inhalation of cigarette smoke. Methods: Twenty Wistar rats were divided into two groups: Cigarette Clot Group (CCG), which in the inhalation chamber received the smoke of 10 cigarettes, 3 times a day, 10 minutes, for 30 days and had the surgical cavity filled by clot; Cigarette Biomaterial Group (CBG), submitted to the same inhalation technique but with the cavity filled by biomaterial. Results: In CCG there was a significant difference of new bone tissue in the analyzed periods (15 and 45 days), and in 15 days, there was 4.8 ± 0.42 of bone formed and 11.73 ± 0.59 (p <0.05) in 45 days. The CBG also showed a significant difference between the periods of 15 to 45 days, being respectively 6.16 ± 0.30 and 11.60 ± 0.61. However, when the groups were compared, within the same analyzed periods, a significant difference was observed only in the period of 15 days, with the new bone percentage being greater in the CBG. Conclusion: The bone matrix acted as an osteoinductive biomaterial, biocompatible and aided in the repair process, mainly in the initial period of recovery.


Subject(s)
Animals , Male , Bone Regeneration/drug effects , Bone Regeneration/physiology , Bone Substitutes/pharmacology , Cigarette Smoking/adverse effects , Osteogenesis/drug effects , Osteogenesis/physiology , Tibia/surgery , Tibia/drug effects , Tibia/physiology , Time Factors , Cattle , Random Allocation , Reproducibility of Results , Bone Transplantation/methods , Treatment Outcome , Rats, Wistar , Inhalation Exposure/adverse effects , Heterografts/physiology
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