Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
1.
J Mater Sci Mater Med ; 29(8): 119, 2018 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-30030632

RESUMEN

Strontium (Sr) has shown effectiveness for stimulating bone remodeling. Nevertheless, the exact therapeutic values are not established yet. Authors hypothesized that local application of Sr-enriched ceramics would enhance bone remodeling in constant osteoporosis of rabbits' femoral neck bone. Seven different bone conditions were analyzed: ten healthy rabbits composed a control group, while other twenty underwent ovariectomy and were divided into three groups. Bone defect was filled with hydroxyapatite 30% (HAP) and tricalcium phosphate 70% (TCP) granules in 7 rabbits, 5% of Sr-enriched HAP/TCP granules in 7, but sham defect was left unfilled in 6 rabbits. Bone samples were obtained from operated and non-operated legs 12 weeks after surgery and analyzed by histomorphometry and immunohistochemistry (IMH). Mean trabecular bone area in control group was 0.393 mm2, in HAP/TCP - 0.226 mm2, in HAP/TCP/Sr - 0.234 mm2 and after sham surgery - 0.242 mm2. IMH revealed that HAP/TCP/Sr induced most noticeable increase of nuclear factor kappa beta 105 (NFkB 105), osteoprotegerin (OPG), osteocalcin (OC), bone morphogenetic protein 2/4 (BMP 2/4), collagen type 1α (COL-1α), interleukin 1 (IL-1) with comparison to intact leg; NFkB 105 and OPG rather than pure HAP/TCP or sham bone. We concluded that Sr-enriched biomaterials induce higher potential to improve bone regeneration than pure bioceramics in constant osteoporosis of femoral neck bone. Further studies on bigger osteoporotic animals using Sr-substituted orthopedic implants for femoral neck fixation should be performed to confirm valuable role in local treatment of osteoporotic femoral neck fractures in humans.


Asunto(s)
Regeneración Ósea/efectos de los fármacos , Sustitutos de Huesos/química , Cerámica/química , Fémur/química , Osteoporosis/terapia , Estroncio/química , Animales , Materiales Biocompatibles/química , Remodelación Ósea , Fosfatos de Calcio/química , Durapatita/química , Femenino , Cabeza Femoral/patología , Inmunohistoquímica , Inflamación , Osteoprotegerina/química , Conejos
2.
Orthod Craniofac Res ; 19(4): 198-208, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27647720

RESUMEN

OBJECTIVES: To test the following two hypotheses: 1) different types of retainers result in distinct levels of biomarkers in gingival crevicular fluid (GCF) and 2) the retainer bonded to all mandibular anterior teeth induces more detrimental outcomes to the periodontium. SETTING AND SAMPLE POPULATION: The Department of Orthodontics at the University of Florida. The population consisted of individuals in the retention phase of orthodontic treatment. MATERIAL AND METHODS: This was a cross-sectional study that enrolled 36 individuals. Subjects in group 1 had retainers bonded to the mandibular canines only. Group 2 consisted of individuals having retainers bonded to all mandibular anterior teeth. Group 3 included patients using mandibular removable retainers. After clinical examination, GCF was collected from the mandibular incisor and biomarker levels were compared between the groups. RESULTS: Plaque accumulation and gingivitis differed significantly among groups, with the highest median values in group 2 subjects. Pairwise comparison of the groups with respect to gingivitis showed significant differences between groups 1 and 2. Significant differences among groups were detected for RANKL, OPG, OPN, M-CSF, MMP-3, and MMP-9. The ratio RANKL/OPG was significantly higher in group 2 subjects, with pairwise comparisons indicating that groups 1 and 2 differed from group 3. CONCLUSION: An association was found between orthodontic retention groups and GCF biomarker levels, which should be further explored in longitudinal studies. The presence of retainers bonded to all anterior teeth seems to increase plaque accumulation and gingivitis.


Asunto(s)
Biomarcadores/química , Recubrimiento Dental Adhesivo/efectos adversos , Recubrimiento Dental Adhesivo/métodos , Placa Dental/etiología , Líquido del Surco Gingival/química , Recesión Gingival/etiología , Gingivitis/etiología , Incisivo/patología , Incisivo/fisiopatología , Retenedores Ortodóncicos/efectos adversos , Adolescente , Adulto , Estudios Transversales , Diente Canino , Índice de Placa Dental , Femenino , Humanos , Proteína Antagonista del Receptor de Interleucina 1/química , Interleucina-1beta/química , Interleucina-6/química , Interleucina-8/química , Factor Estimulante de Colonias de Macrófagos/química , Masculino , Mandíbula , Metaloproteinasa 3 de la Matriz/química , Metaloproteinasa 9 de la Matriz/química , Persona de Mediana Edad , Diseño de Aparato Ortodóncico , Osteopontina/química , Osteoprotegerina/química , Índice Periodontal , Ligando RANK/química
3.
Biomacromolecules ; 16(8): 2374-81, 2015 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-26151628

RESUMEN

Polymers of similar molecular weights and chemical constitution but varying in their macromolecular architectures were conjugated to osteoprotegerin (OPG) to determine the effect of polymer topology on protein activity in vitro and in vivo. OPG is a protein that inhibits bone resorption by preventing the formation of mature osteoclasts from the osteoclast precursor cell. Accelerated bone loss disorders, such as osteoporosis, rheumatoid arthritis, and metastatic bone disease, occur as a result of increased osteoclastogenesis, leading to the severe weakening of the bone. OPG has shown promise as a treatment in bone disorders; however, it is rapidly cleared from circulation through rapid liver uptake, and frequent, high doses of the protein are necessary to achieve a therapeutic benefit. We aimed to improve the effectiveness of OPG by creating OPG-polymer bioconjugates, employing reversible addition-fragmentation chain transfer polymerization to create well-defined polymers with branching densities varying from linear, loosely branched to densely branched. Polymers with each of these architectures were conjugated to OPG using a "grafting-to" approach, and the bioconjugates were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The OPG-polymer bioconjugates showed retention of activity in vitro against osteoclasts, and each bioconjugate was shown to be nontoxic. Preliminary in vivo studies further supported the nontoxic characteristics of the bioconjugates, and measurement of the bone mineral density in rats 7 days post-treatment via peripheral quantitative computed tomography suggested a slight increase in bone mineral density after administration of the loosely branched OPG-polymer bioconjugate.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Resorción Ósea/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Osteoprotegerina/química , Animales , Artritis Reumatoide/patología , Densidad Ósea/efectos de los fármacos , Resorción Ósea/patología , Humanos , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Osteoporosis/patología , Osteoprotegerina/administración & dosificación , Polímeros/administración & dosificación , Polímeros/química , Ratas
4.
Pharm Res ; 29(11): 3143-55, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22729371

RESUMEN

PURPOSE: Recombinant osteoprotegerin (OPG) has been proven to be useful for treating various bone disorders such as osteoporosis. To improve its in vivo pharmacological effect, OPG was conjugated to novel comb-shaped co-polymers of polyethylene glycol (PEG) allylmethylether and maleamic acid (poly(PEG), 5 kDa). Biodistribution and bioactivity were evaluated. METHODS: OPG was conjugated via lysine to poly(PEG) and to linear PEG (0.5 kDa and 5 kDa). Poly(PEG)-OPG was compared with linear PEG0.5k-OPG and PEG5k-OPG in terms of in vitro and in vivo efficacy and bone distribution. RESULTS: The in vitro receptor binding study showed that poly(PEG)-OPG could be the most bioactive among the three PEG-OPG derivatives. Pharmacokinetic studies in ovariectomized (OVX) rats showed that serum half-life and AUC of poly(PEG)-OPG were comparable with those of linear PEG-OPG derivatives. For in vivo pharmacological effect, poly(PEG)-OPG showed the strongest inhibitory effect on bone resorption activity in OVX rats. Poly(PEG)-OPG demonstrated enhanced bone marrow distribution with higher selectivity than linear PEG5k-OPG. CONCLUSION: Poly(PEG) modification could provide longer residence time in serum and higher bone-marrow specific delivery of OPG, leading to a higher in vivo pharmacological effect.


Asunto(s)
Huesos/efectos de los fármacos , Huesos/metabolismo , Osteoclastos/efectos de los fármacos , Osteoprotegerina/administración & dosificación , Osteoprotegerina/química , Polietilenglicoles/administración & dosificación , Administración Intravenosa , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Femenino , Humanos , Maleatos/administración & dosificación , Maleatos/química , Osteoclastos/metabolismo , Osteoprotegerina/farmacocinética , Ovariectomía/métodos , Polietilenglicoles/química , Polímeros/administración & dosificación , Polímeros/química , Ratas , Ratas Endogámicas F344 , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacocinética , Relación Estructura-Actividad , Distribución Tisular
5.
J Mater Sci Mater Med ; 21(2): 647-53, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19834789

RESUMEN

The purpose of the present study was to examine the effect of osteoprotegerin (OPG)-Fc fusion protein immobilized on a titanium surface on the initial differentiation of osteoclast precursor RAW264.7 cells. These cells were cultured on titanium specimens over which OPG-Fc was immobilized. The enhancement of tartrate-resistant acid phosphatase (TRAP) and cathepsin K mRNA expression in RAW264.7 cells exposed to receptor activator of NF-kappaB ligand (RANKL) stimulation on OPG-Fc-coated titanium was significantly lower than that in RAW264.7 cells exposed to RANKL on titanium specimens without immobilized OPG-Fc (ANOVA, P < 0.01). Preincubation of OPG-Fc-coated titanium, in a medium supplemented with 10% fetal bovine serum at 37 degrees C for two days before the cells were seeded, had no significant effect on the decrease in mRNA expression (ANOVA, P < 0.01). Taken together, these results indicate that OPG-Fc immobilized on a titanium surface blocks the differentiation of RAW264.7 cells induced by RANKL stimulation.


Asunto(s)
Materiales Biocompatibles Revestidos/farmacología , Macrófagos/citología , Macrófagos/metabolismo , Osteoclastos/citología , Osteoclastos/metabolismo , Osteoprotegerina/química , Osteoprotegerina/farmacología , Ligando RANK/metabolismo , Titanio/química , Adsorción , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular , Materiales Biocompatibles Revestidos/química , Fragmentos Fc de Inmunoglobulinas/química , Fragmentos Fc de Inmunoglobulinas/farmacología , Macrófagos/efectos de los fármacos , Ensayo de Materiales , Ratones , Osteoclastos/efectos de los fármacos , Propiedades de Superficie
6.
Med Hypotheses ; 94: 40-2, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27515196

RESUMEN

Chronic inflammatory processes in periapical tissues caused by etiological agents of endodontic origin lead to apical periodontitis. Apart from bacteria, two herpesviruses, Epstein-Barr virus (EBV) and Human cytomegalovirus (HCMV) are recognized as putative pathogens in apical periodontitis. Although previous reports suggest the involvement of EBV in the pathogenesis of apical periodontitis, its exact role in periapical bone resorption has not yet been fully elucidated. We hypothesize that EBV infection in apical periodontitis is capable of inducing periapical bone resorption via stimulation of reactive oxygen species (ROS) overproduction. Increased levels of ROS induce expression of receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). RANKL binding to receptor activator of nuclear factor κB (RANK) present on the surface of preosteoclasts induces their maturation and activation which consequently leads to bone resorption. The potential benefit of antiviral and antioxidant-based therapies in periapical bone resorption treatment remains to be assessed.


Asunto(s)
Resorción Ósea , Infecciones por Virus de Epstein-Barr/fisiopatología , Periodontitis Periapical/patología , Especies Reactivas de Oxígeno/metabolismo , Animales , Linfocitos B/citología , Células Epiteliales/citología , Herpesvirus Humano 4 , Humanos , Inflamación , Modelos Teóricos , Osteoclastos/citología , Osteoprotegerina/química , Periodontitis Periapical/fisiopatología , Ligando RANK/metabolismo , Receptor Activador del Factor Nuclear kappa-B/metabolismo
7.
Angle Orthod ; 86(2): 187-92, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26154939

RESUMEN

OBJECTIVE: To carry out an immunoassay analysis of biomarkers expressed in gingival crevicular fluid (GCF) with the main goal of finding a useful diagnostic pattern to distinguish between resorbing deciduous teeth and nonresorbing controls. MATERIALS AND METHODS: A split-mouth design was used in this study with a total of 22 GCF samples collected from 11 patients in the mixed dentition. For each child, one deciduous molar with radiographic evidence of root resorption was used as the test tooth whereas the contralateral first permanent molar with formed roots was used as the control tooth. Samples were processed with immunoassays using a panel of selected biomarkers including interleukin-1 beta (IL-1b), interleukin-1 receptor antagonist (IL-1RA), nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase-9 (MMP-9), and dentin sialoprotein (DSP). RESULTS: There were no statistically significant differences in levels of IL-1b, OPG, and MMP-9 between test and control sites (P > .05). IL-1RA was the only biomarker to show a significant down-regulation (P  =  .04) in GCF samples collected from resorbing teeth. RANKL data showed a heavily skewed distribution and was deemed unreliable. Only one deciduous GCF sample had detectable levels of DSP; therefore, no further statistical calculation was applicable because of the limited amount of data for this biomarker. CONCLUSIONS: This study indicated that IL1-RA is down-regulated in GCF from resorbing primary molars, thus suggesting this cytokine as a potential analyte to be included in a panel that can discriminate between resorbing and nonresorbing teeth.


Asunto(s)
Biomarcadores/química , Líquido del Surco Gingival/química , Inmunoensayo , Proteína Antagonista del Receptor de Interleucina 1/química , Resorción Radicular/diagnóstico , Niño , Proteínas de la Matriz Extracelular/química , Humanos , Interleucina-1beta/química , Metaloproteinasa 9 de la Matriz/química , Diente Molar , Osteoprotegerina/química , Fosfoproteínas/química , Ligando RANK/química , Sialoglicoproteínas/química
9.
J Pharm Pharmacol ; 62(8): 985-94, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20663032

RESUMEN

OBJECTIVES: Our aim was to investigate the effect of PEGylation on the uptake of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) into rat liver, kidney and spleen, and human liver. METHODS: Copolymer of polyethyleneglycol allylmethylether and maleamic acid sodium salt with OCIF (poly(PEG)-OCIF) (0.5 mg/kg) was administered to rats and the concentrations of poly(PEG)-OCIF in the liver, kidney and spleen at 15 min after administration were measured by ELISA. For human liver uptake, the liver perfusion of OCIF and (3)H-labelled poly(PEG)-OCIF was conducted using fresh human liver block. KEY FINDINGS: The tissue uptake of poly(PEG)-OCIF in rats was significantly lower compared with that of OCIF. In fresh human liver perfusion, (3)H-poly(PEG)-OCIF was rarely taken up into the liver. On the other hand, more than 50% of the perfused OCIF was taken up. CONCLUSIONS: PEGylation of OCIF using poly(PEG) dramatically suppressed the uptake of OCIF into human liver as well as into rat liver and could be a promising approach for improving the pharmacokinetic and pharmacological effects of OCIF in the clinical setting.


Asunto(s)
Conservadores de la Densidad Ósea/farmacocinética , Hígado/metabolismo , Osteoprotegerina/farmacocinética , Polietilenglicoles/química , Animales , Transporte Biológico , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/sangre , Conservadores de la Densidad Ósea/química , Células Cultivadas , Química Farmacéutica , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática , Femenino , Heparina/metabolismo , Humanos , Inyecciones Intravenosas , Riñón/metabolismo , Maleatos/química , Ratones , Osteoclastos/efectos de los fármacos , Osteoprotegerina/administración & dosificación , Osteoprotegerina/sangre , Osteoprotegerina/química , Ovariectomía , Perfusión , Ratas , Ratas Sprague-Dawley , Bazo/metabolismo , Distribución Tisular
10.
J Biomed Mater Res A ; 84(4): 965-72, 2008 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-17647240

RESUMEN

Strontium is known to reduce bone resorption and stimulate bone formation. We have investigated the effect of strontium on the setting properties and in vitro bioactivity of a biomimetic gelatin-calcium phosphate bone cement. Gelatin-alpha-TCP powders, with a gelatin content of 15 wt %, were prepared by grinding and sieving the solid compounds obtained by casting gelatin aqueous solutions containing alpha-TCP. 5 wt % of CaHPO(4).2H(2)O were added to the cement powders before mixing with the liquid phase, with a L/P ratio of 0.3 mL/g. Strontium was added as SrCl(2).6H(2)O in different amounts up to 5 atom %. X-ray diffraction analysis, mechanical tests, and SEM investigations were carried out on the cements after different times of soaking in physiological solution. The presence of strontium affects both the initial and the final setting times of the cements, which increase with the ion content. The microstructural modifications observed in the SEM micrographs of the fractured surfaces are in agreement with the increase of the total porosity, and with the slight reduction of the compressive strength of the aged cements, on increasing strontium content. The rate of transformation of alpha-TCP into calcium deficient hydroxyapatite increases on increasing strontium content. SEM reveals that MG63 osteoblasts grown on the cements show a normal morphology and biological tests demonstrate very good rate of proliferation and viability in every experimental time. In particular, strontium stimulates Alkaline Phosphatase activity, Collagen type I, osteocalcin, and osteoprotegerin expression.


Asunto(s)
Materiales Biocompatibles/química , Cementos para Huesos/química , Fosfatos de Calcio/química , Gelatina/química , Estroncio/química , Fosfatasa Alcalina/metabolismo , Animales , Adhesión Celular , Colágeno Tipo I/metabolismo , Humanos , Osteocalcina/química , Osteoprotegerina/química , Polvos , Porcinos
11.
Acta Biomater ; 4(6): 1885-93, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18554996

RESUMEN

The increasing interest in strontium incorporation into biomaterials for hard tissue repair is justified by the growing evidence of its beneficial effect on bone. We successfully synthesized hydroxyapatite (HA) thin films with different extents of strontium substitution for calcium (0, 1, 3 or 7 at.%) by pulsed-laser deposition. The coatings displayed a granular surface and a good degree of crystallinity, which slightly diminished as strontium content increased. Osteoblast-like MG63 cells and human osteoclasts were cultured on the thin films up to 21 days. MG63 cells grown on the strontium-doped HA coatings displayed normal morphology, good proliferation and increased values of the differentiation parameters, whereas the number of osteoclasts was negatively influenced by the presence of strontium. The positive effect of the ion on bone cells was particularly evident in the case of coatings deposited from HA at relatively high strontium contents (3-7%), where significantly increased values of alkaline phosphatase activity, osteocalcin, type I collagen and osteoprotegerin/TNF-related activation-induced cytokine receptor ratio, and considerably reduced values of osteoclast proliferation, were observed.


Asunto(s)
Materiales Biocompatibles/química , Hidroxiapatitas/química , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Estroncio/química , Fosfatasa Alcalina/metabolismo , Calcio/química , Diferenciación Celular , Proliferación Celular , Colágeno Tipo I/química , Humanos , Técnicas In Vitro , Rayos Láser , Nanopartículas/química , Nanotecnología/métodos , Osteocalcina/química , Osteoprotegerina/química , Factor de Necrosis Tumoral alfa/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA