RESUMEN
Dried plum has been reported to have potent effects on bone in osteopenic animal models, but the mechanisms through which bone metabolism is altered in vivo remain unclear. To address this issue, a study comparing the metabolic response of dried plum to the anabolic agent, parathyroid hormone (PTH), was undertaken. Six month-old female Sprague Dawley rats (n=84) were sham-operated (SHAM) or ovariectomized (OVX) and maintained on a control diet for 6wks until osteopenia was confirmed. Treatments were initiated consisting of a control diet (AIN-93M) supplemented with dried plum (0, 5, 15 or 25%; w/w) or a positive control group receiving PTH. At the end of 6wks of treatment, whole body and femoral bone mineral density (BMD) were restored by the two higher doses of dried plum to the level of the SHAM group. Trabecular bone volume and cortical thickness were also improved with these two doses of dried plum. Dried plum suppressed the OVX-induced increase in bone turnover as indicated by systemic biomarkers of bone metabolism, N-terminal procollagen type 1 (P1NP) and deoxypyridinoline (DPD). Dynamic bone histomorphometric analysis of the tibial metaphysis revealed that dried plum restored the OVX-induced increase in cancellous bone formation rate (BFR) and mineralizing surface (MS/BS) to the SHAM group, but some doses of dried plum increased endocortical mineral apposition rate (MAR). As expected, PTH significantly increased endocortical MAR and BFR, periosteal BFR, and trabecular MAR and BFR beyond that of the OVX and maintained the accelerated rate of bone resorption associated with OVX. Dried plum up-regulated bone morphogenetic protein 4 (Bmp4) and insulin-like growth factor 1 (Igf1) while down-regulating nuclear factor T cell activator 1 (Nfatc1). These findings demonstrate that in the adult osteopenic OVX animal, the effects of dried plum differ from that of PTH in that dried plum primarily suppressed bone turnover with the exception of the indices of bone formation at the endocortical surface.
Asunto(s)
Enfermedades Óseas Metabólicas/tratamiento farmacológico , Huesos/metabolismo , Suplementos Dietéticos , Ovariectomía , Hormona Paratiroidea/uso terapéutico , Extractos Vegetales/uso terapéutico , Prunus/química , Animales , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/metabolismo , Enfermedades Óseas Metabólicas/fisiopatología , Huesos/efectos de los fármacos , Huesos/patología , Huesos/fisiopatología , Densitometría , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Hormona Paratiroidea/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Tibia/diagnóstico por imagen , Tibia/efectos de los fármacos , Tibia/metabolismo , Tibia/fisiopatología , Útero/efectos de los fármacos , Útero/patología , Microtomografía por Rayos XRESUMEN
Bone minerals possess two primary hydrogen sources: hydroxide ions in the nanocrystalline core and structural water in the amorphous surface layer. In order to accurately measure their concentrations using hydrogen to phosphorus cross polarization NMR spectroscopy, it is necessary to analyze the dependence of signal intensities on serial contact times, namely, cross polarization kinetics. A reliable protocol is developed to iteratively decompose the severely overlapped spectra and to analyze the cross-polarization kinetics, leading to measurement of hydroxyl and structural water concentrations. Structural water concentration is used to estimate mineral specific surface area and nanocrystal thickness for intact bone.
RESUMEN
Interest in dried plum has increased over the past decade due to its promise in restoring bone and preventing bone loss in animal models of osteoporosis. This study compared the effects of dried plum on bone to other dried fruits and further explored the potential mechanisms of action through which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) C57BL/6 mice were fed either a control diet or a diet supplemented with 25% (w/w) dried plum, apple, apricot, grape or mango for 8 weeks. Whole body and spine bone mineral density improved in mice consuming the dried plum, apricot and grape diets compared to the OVX control mice, but dried plum was the only fruit to have an anabolic effect on trabecular bone in the vertebra and prevent bone loss in the tibia. Restoration of biomechanical properties occurred in conjunction with the changes in trabecular bone in the spine. Compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation coincident with up-regulating osteoblast and glutathione (GPx) activity. These alterations in bone metabolism and antioxidant status compared to other dried fruits provide insight into dried plum's unique effects on bone.
Asunto(s)
Densidad Ósea , Huesos/fisiopatología , Frutas , Osteoporosis Posmenopáusica/dietoterapia , Osteoporosis Posmenopáusica/fisiopatología , Prunus , Animales , Apoptosis , Fenómenos Biomecánicos , Peso Corporal , Huesos/metabolismo , Huesos/patología , Diferenciación Celular , Dieta/métodos , Femenino , Frutas/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Osteoblastos/metabolismo , Osteoblastos/patología , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/patología , Prunus/metabolismoRESUMEN
Iron deficiency (ID) remains a public health concern affecting ~25% of the world's population. Metabolic consequences of ID include elevated plasma glucose concentrations consistent with increased reliance on glucose as a metabolic substrate, though the mechanisms controlling these responses remain unclear. To further characterize the metabolic response to ID, weanling male Sprague-Dawley rats were fed either a control (C; 40 mg Fe/kg diet) or iron-deficient (ID; 3 mg Fe/kg diet) diet or were pair-fed (PF) the C diet to the level of intake of the ID group for 21 days. In addition to reductions in hemoglobin, hematocrit, and plasma iron, the ID group also exhibited higher percent body fat and plasma triglycerides compared to the PF group. Steady-state levels of both plasma glucose and insulin increased 40 and 45%, respectively, in the ID group compared to the PF group. Plasma cortisol levels were decreased 67% in the ID group compared to the PF diet group. The systematic evaluation of the expression of genes involved in insulin signaling, glucose metabolism, and fatty acid metabolism in the liver and skeletal muscle revealed significant alterations in the expression of 48 and 52 genes in these tissues, respectively. A significant concurrent increase in lipogenic gene expression and decrease in gene expression related to ß-oxidation in both the liver and skeletal muscle, in combination with differential tissue expression of genes involved in glucose metabolism, provides novel insight into the adaptive metabolic response in rodent models of severe iron deficiency anemia.
RESUMEN
This study was designed to investigate the effects of dried plum on the changes in bone metabolism and the immune response associated with ovarian hormone deficiency. Adult female C57BL/6J mice were either sham-operated (Sham) and fed AIN-93 diet (control) or ovariectomized (OVX) and fed a control diet with 0%, 5%, 15% or 25% dried plum (w/w), corresponding to control, low- (LDP), medium- (MDP) and high (HDP)-dose dried plum. Four weeks of HDP supplementation prevented the decrease in spine bone mineral density and content induced by OVX. The OVX compromise in trabecular bone of the vertebra and proximal tibia was prevented by the higher doses of dried plum, and in the vertebra these effects resulted in greater (P<.05) bone strength and stiffness. In the bone marrow, OVX suppressed granulocyte and committed monocyte populations and increased the lymphoblast population, but the MDP and HDP restored these myeloid and lymphoid populations to the level of the Sham. Dried plum also suppressed lymphocyte tumor necrosis factor (TNF)-α production ex vivo by splenocytes, in response to concanavalin (Con) A stimulation. These data indicate that dried plum's positive effects on bone structural and biomechanical properties coincide with the restoration of certain bone marrow myeloid and lymphoid populations, and suppressed splenocyte activation occurring with ovarian hormone deficiency.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Suplementos Dietéticos , Osteoporosis/inmunología , Osteoporosis/prevención & control , Prunus , Animales , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Células de la Médula Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Concanavalina A/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Ingestión de Alimentos , Femenino , Fémur , Expresión Génica , Factor I del Crecimiento Similar a la Insulina/metabolismo , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos/efectos de los fármacos , Ovariectomía , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Tibia/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Útero/efectos de los fármacosRESUMEN
Iron regulatory proteins (IRP) regulate cellular iron metabolism by binding to iron-responsive elements (IRE) located in untranslated regions of mRNA-encoding proteins of iron metabolism. Recently, IRE have been identified in mRNA-encoding proteins with previously uncharacterized roles in iron metabolism, thus expanding the role of IRP beyond the regulation of cellular iron homeostasis. The mRNA for HIF 2-α contains an IRE and undergoes iron-dependent regulation in vitro, though the translational regulation of HIF-2α in vivo remains unknown. To examine HIF-2α translational regulation in vivo, we evaluated the effects of iron deficiency on the regulation of hepatic IRP activity and HIF-2α translation. Rats were fed either a control (C; 50 mg Fe/kg diet) or iron-deficient (ID; <5 mg Fe/kg diet) diet or were pair-fed (PF) the C diet for 21 d. In ID rats, there was a 2-fold increase in IRP activity compared to the PF group (P < 0.05), which was reflected by a 30-40% increase in HIF-2α repression (P < 0.05). In agreement with a decrease in translation, the levels of HIF-2α proteins were also decreased. The relative abundance of HIF-2α mRNA did not differ between treatment groups. Taken together, these results suggest that the translation of HIF-2α in the liver is regulated in part by the action of IRP in response to dietary iron deficiency and provide evidence that IRP may assist in coordinating the cellular response to alterations in iron and oxygen status associated with iron deficiency anemia.