RESUMEN

Reliable gene expression analysis in bone remodeling studies requires an appropriate selection of internal controls, i.e. stable reference genes for the normalization of quantitative real-time PCR (RT-qPCR), the most common method used for quantifying gene expression measurements. Even the most widely used reference genes can have variable expression under different experimental conditions, or in different tissue types or treatment regimes, so selecting appropriate controls is a key step in ensuring reliable results. The aim of this research was to identify the most stable reference gene(s) for the study of olanzapine modulated bone remodeling in rats. RNA was isolated from the maxillary alveolar and femoral bones of olanzapine or placebo-treated Wistar rats and transcribed to cDNA. The expression of 12 candidate reference genes was assessed by RT-qPCR. Their expressions were analysed using GeNorm, NormFinder, BestKeeper and delta Ct algorithms, and by the comprehensive ranking method. PPIA, HRPT1 and PGK1 were the most stably expres sed reference genes and the combination of the three genes was optimal for normalization. This study is the first to identify the optimal reference genes for research in olanzapine-exposed rats, which serve as a pivotal benchmark for enhancing the accuracy and reliability of future RT-qPCR expression in bone studies.

Asunto(s)

Remodelación Ósea , Fémur , Olanzapina , Fosfoglicerato Quinasa , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Animales , Olanzapina/farmacología , Ratas , Fémur/efectos de los fármacos , Fémur/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Masculino , Remodelación Ósea/efectos de los fármacos , Remodelación Ósea/genética , Fosfoglicerato Quinasa/genética , Perfilación de la Expresión Génica/métodos , Reproducibilidad de los Resultados , Antipsicóticos/farmacología

RESUMEN

BACKGROUND: Bisphosphonate (BP) can treat osteoporosis and prevent osteoporotic fractures in clinical. However, the effect of BP on microstructure and mechanical properties of cortical and trabecular bone has been taken little attention, separately. METHODS: In this study, BP was used to intervene in ovariectomized female SD rats. The femoral micro-CT images were used to measure the structural parameters and reconstruct the 3D models in volume of interest. The structural parameters of cortical and trabecular bone were measured, and the mechanical properties were predicted using micro-finite element analysis. RESULTS: There was almost no significant difference in the morphological structure parameters and mechanical properties of cortical bone between normal, ovariectomized (sham-OVX) and BP intervention groups. However, BP could significantly improve bone volume fraction (BV/TV) and trabecular separation (Tb.SP) in inter-femoral condyles (IT) (sham-OVX vs. BP, p < 0.001), and had no significant effect on BV/TV in medial and lateral femoral condyles (MT, LT). Similarly, BPs could significantly affect the effective modulus in IT (sham-OVX vs. BP, p < 0.001), and had no significant difference in MT and LT. In addition, the structural parameters and effective modulus showed a good linear correlation. CONCLUSION: In a short time, the effects of BP intervention and osteoporosis on cortical bone were not obvious. The effects of BP on trabecular bone in non-main weight-bearing area (IT) were valuable, while for osteoporosis, the main weight-bearing area (MT, LT) may improve the structural quality and mechanical strength of trabecular bone through exercise compensation.

Asunto(s)

Difosfonatos , Osteoporosis , Ovariectomía , Ratas Sprague-Dawley , Microtomografía por Rayos X , Animales , Femenino , Osteoporosis/tratamiento farmacológico , Osteoporosis/diagnóstico por imagen , Difosfonatos/farmacología , Difosfonatos/uso terapéutico , Ratas , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Fémur/efectos de los fármacos , Fémur/diagnóstico por imagen , Fémur/patología , Fémur/fisiopatología , Hueso Esponjoso/efectos de los fármacos , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/patología , Fenómenos Biomecánicos , Modelos Animales de Enfermedad , Densidad Ósea/efectos de los fármacos , Análisis de Elementos Finitos

RESUMEN

This study looked at how desalinated seawater, which has low minerals and high boron, could affect bone health. Prior research suggests that low mineral water may harm bone health and boron could be beneficial, but the overall impact on bone health is still unclear. Eighty-nine-week-old male Balb/C mice were allocated into eight groups and administered either tap water or purified water with varying boron concentrations (0, 5, 40, and 200 mg/L). They were kept in an environment mimicking tropical conditions (35-40 °C, 70-80% humidity) and underwent daily treadmill exercise for 13 weeks. At the 14th week, serum, femora, and lumbar vertebrae were collected for mineral metabolism, bone biomarker, microstructure, and biomechanics evaluation. Boron exposure improved bone formation, microstructure, and biomechanics initially but the benefits weakened with higher levels of exposure (p < 0.05). Co-exposure to purified water elevated serum boron but weakened the promotion of boron on bone minerals and the bone benefits of boron compared to tap water (p < 0.05). Thus, when studying the health effects of boron in desalinated seawater, it is crucial to look at various health effects beyond bone health. Furthermore, it is important to consider the mineral composition of drinking water when using boron for bone health benefits.

Asunto(s)

Huesos , Boro , Ratones Endogámicos BALB C , Aguas Minerales , Agua de Mar , Animales , Boro/farmacología , Masculino , Agua de Mar/química , Ratones , Huesos/efectos de los fármacos , Huesos/metabolismo , Densidad Ósea/efectos de los fármacos , Agua Potable , Biomarcadores/sangre , Vértebras Lumbares/efectos de los fármacos , Fémur/efectos de los fármacos

RESUMEN

The borosilicate 0106-B1-bioactive glass (BG) composition (in wt%: 37.5 SiO2, 22.6 CaO, 5.9 Na2O, 4.0P2O5, 12.0 K2O, 5.5 MgO, 12.5 B2O3) has shown favorable processing characteristics and bone regeneration ability. This study investigated the addition of zinc (Zn) to 0106-B1-BG as an approach to improve this BG's biological properties. Different proportions of ZnO were substituted for CaO in 0106-B1-BG, resulting in three new BG-compositions: 1-Zn-BG, 2-Zn-BG, 3-Zn-BG (in wt%: 37.5 SiO2, 21.6/20.1/17.6 CaO, 4.0 P2O5, 5.9 Na2O, 12.0 K2O, 5.5 MgO, 12.5 B2O3 and 1.0/2.5/5.0 ZnO). Effects of the BG compositions on cytocompatibility, osteogenic differentiation, extracellular matrix deposition, and angiogenic response of human bone marrow-derived mesenchymal stromal cells (BMSCs) were evaluated in vitro. Angiogenic effects were assessed using a tube formation assay containing human umbilical vein endothelial cells. The in vivo osteogenic and angiogenic potentials of 3-Zn-BG were investigated in comparison to the Zn-free 0106-B1-BG in a rodent critical-size femoral defect model. The osteogenic differentiation of BMSCs improved in the presence of Zn. 3-Zn-BG showed enhanced angiogenic potential, as confirmed by the tube formation assay. While Zn-doped BGs showed clearly superior biological properties in vitro, 3-Zn-BG and 0106-B1-BG equally promoted the formation of new bone in vivo; however, 3-Zn-BG reduced osteoclastic cells and vascular structures in vivo. The acquired data suggests that the differences regarding the in vivo and in vitro results may be due to modulation of inflammatory responses by Zn, as described in the literature. The inflammatory effect should be investigated further to promote clinical applications of Zn-doped BGs.

Asunto(s)

Fémur , Vidrio , Células Madre Mesenquimatosas , Osteogénesis , Silicatos , Zinc , Animales , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Ratas , Zinc/química , Zinc/farmacología , Silicatos/química , Silicatos/farmacología , Fémur/efectos de los fármacos , Fémur/patología , Vidrio/química , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Ratas Sprague-Dawley , Masculino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Regeneración Ósea/efectos de los fármacos

RESUMEN

Vitamin A derivatives have inhibitory effects on cartilage tissue, such as decreasing chondrocyte proliferation and collagen synthesis, and increasing the loss of glycosaminoglycans and proteoglycans. Therefore, isotretinoin (a vitamin A derivative) may play a role in the pathogenesis of cartilage-related diseases like osteoarthritis by affecting the balance of cartilage tissue. The aim of this study was to evaluate the distal femoral cartilage thickness in acne patients under the systemic isotretinoin therapy and to determine whether it constitutes a risk factor for the development of osteoarthritis. The study included 52 patients (42 female, 10 male, mean age 23.31 ± 3.89 years) who were prescribed systemic isotretinoin for acne and completed at least 3 months of treatment, along with 45 healthy controls ((35 female, 10 male, mean age 23.85 ± 4.77 years). Bilateral distal femoral cartilage thickness was measured by ultrasonography before isotretinoin treatment and after the completion of the third month of treatment. After treatment, a statistically significant increase was found in the thickness of the right medial, right lateral, left medial, left lateral, and left intercondylar cartilage (p = 0.014, 0.012, 0.019, 0.027, 0.002, respectively). There was also an increase in the right intercondylar cartilage thickness, but this was not statistically significant (p = 0.1). Systemic isotretinoin seems to make cartilage thicker. The increase in femoral cartilage thickness observed after short-term isotretinoin treatment might be an indicator of very early-stage osteoarthritis. Extended follow-up studies with larger participant pools are necessary to substantiate this result.

Asunto(s)

Acné Vulgar , Cartílago Articular , Fémur , Isotretinoína , Humanos , Isotretinoína/efectos adversos , Isotretinoína/uso terapéutico , Isotretinoína/administración & dosificación , Femenino , Masculino , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/patología , Acné Vulgar/diagnóstico , Adulto , Adulto Joven , Cartílago Articular/patología , Cartílago Articular/efectos de los fármacos , Cartílago Articular/diagnóstico por imagen , Fémur/diagnóstico por imagen , Fémur/efectos de los fármacos , Fémur/patología , Ultrasonografía , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Osteoartritis/diagnóstico por imagen , Factores de Riesgo , Estudios de Casos y Controles

RESUMEN

Drug use during pregnancy is an important issue that must be investigated due to its adverse effects on maternal and foetal health. This study aimed to determine the embryotoxic and teratogenic effects of in-ovo administered metamizole (dipyrone), which can be used when needed during pregnancy and has potent analgesic, antipyretic, anti-inflammatory, and long bone (tibia and femur) effects. This study used 240 fertile eggs from Atak S breed chickens, divided into eight equal groups: control, vehicle control, and 15.62, 31.25, 62.5, 125, 250 and 500 mg/kg metamizole. The eggs were hatched on the 21st day of incubation, and the chicks' body weights and mortality rates were determined. The right and left femur and tibia bones were resected from the chicks. Anatomical reference points were determined after removing the soft tissues of the bones, and necessary morphometric measures were taken from these points with a 0.01 mm precision using digital callipers. The 100% lethal dose (LD100) was identified in the highest examined dose (500 mg/kg) in the Chicken Embryotoxicity Screening Test (CHEST)-I stage. The CHEST-II stage determined the 50% lethal dose (LD50). High-dose metamizole affected skeletal development, significantly decreasing tibia and femur lengths and corpus thicknesses and increasing mortality.

Asunto(s)

Antiinflamatorios no Esteroideos , Pollos , Dipirona , Teratógenos , Animales , Dipirona/toxicidad , Embrión de Pollo/efectos de los fármacos , Antiinflamatorios no Esteroideos/toxicidad , Teratógenos/toxicidad , Fémur/efectos de los fármacos , Fémur/embriología , Tibia/efectos de los fármacos , Femenino

RESUMEN

PURPOSE: The effects of daily teriparatide (D-PTH, 20 µg/day), weekly high-dose teriparatide (W-PTH, 56.5 µg/week), or bisphosphonate (BP) on the vertebra and proximal femur were investigated using quantitative computed tomography (QCT). METHODS: A total of 131 postmenopausal women with a history of fragility fractures were randomized to receive D-PTH, W-PTH, or bisphosphonate (oral alendronate or risedronate). QCT were evaluated at baseline and after 18 months of treatment. RESULTS: A total of 86 participants were evaluated by QCT (Spine: D-PTH: 25, W-PTH: 21, BP: 29. Hip: PTH: 22, W-PTH: 21, BP: 32. Dropout rate: 30.5 %). QCT of the vertebra showed that D-PTH, W-PTH, and BP increased total vBMD (+34.8 %, +18.2 %, +11.1 %), trabecular vBMD (+50.8 %, +20.8 %, +12.2 %), and marginal vBMD (+20.0 %, +14.0 %, +11.5 %). The increase in trabecular vBMD was greater in the D-PTH group than in the W-PTH and BP groups. QCT of the proximal femur showed that D-PTH, W-PTH, and BP increased total vBMD (+2.8 %, +3.6 %, +3.2 %) and trabecular vBMD (+7.7 %, +5.1 %, +3.4 %), while only W-PTH and BP significantly increased cortical vBMD (-0.1 %, +1.5 %, +1.6 %). Although there was no significant increase in cortical vBMD in the D-PTH group, cortical bone volume (BV) increased in all three treatment groups (+2.1 %, +3.6 %, +3.1 %). CONCLUSIONS: D-PTH had a strong effect on trabecular bone of vertebra. Although D-PTH did not increase cortical BMD of proximal femur, it increased cortical BV. W-PTH had a moderate effect on trabecular bone of vertebra, while it increased both cortical BMD and BV of proximal femur. Although BP had a limited effect on trabecular bone of vertebra compared to teriparatide, it increased both cortical BMD and BV of proximal femur.

Asunto(s)

Hueso Esponjoso , Difosfonatos , Fémur , Posmenopausia , Teriparatido , Tomografía Computarizada por Rayos X , Humanos , Teriparatido/administración & dosificación , Teriparatido/uso terapéutico , Teriparatido/farmacología , Femenino , Anciano , Fémur/efectos de los fármacos , Fémur/diagnóstico por imagen , Fémur/patología , Hueso Esponjoso/efectos de los fármacos , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/patología , Difosfonatos/administración & dosificación , Difosfonatos/farmacología , Difosfonatos/uso terapéutico , Posmenopausia/efectos de los fármacos , Hueso Cortical/efectos de los fármacos , Hueso Cortical/diagnóstico por imagen , Hueso Cortical/patología , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/uso terapéutico , Persona de Mediana Edad , Densidad Ósea/efectos de los fármacos , Fracturas Óseas/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/efectos de los fármacos

RESUMEN

Trends toward more favorable improvement of the cortical bone parameters by once-weekly (56.5 µg once a week) and twice-weekly teriparatide (28.2 µg twice a week), and that of the trabecular bone parameters by once-daily (1/D) teriparatide (20 µg/day once a day) were shown. PURPOSE: To examine the effects of differences in the amount of teriparatide (TPTD) per administration and its dosing frequency on the bone structure in the proximal femur by dual-energy X-ray absorptiometry (DXA)-based 3D-modeling (3D-SHAPER software). METHODS: This was a multicenter retrospective study. Patients aged 50 years or older with primary osteoporosis who continuously received once-/twice-weekly (1・2/W, n = 60) or 1/D TPTD (n = 14) administration for at least one year were included in the study. Measurement regions included the femoral neck (FN), trochanter (TR), femoral shaft (FS), and total proximal hip (TH). Concurrently, the bone mineral density (BMD) and Trabecular Bone Score (TBS) were measured. RESULTS: The cross-sectional area, cross-sectional moment of inertia, and section modulus in the FS were significantly improved in the 1・2/W TPTD group, as compared to the 1/D TPTD group. However, significant improvement of the cortical thickness and buckling ratio in the FN was observed in the 1/D TPTD group, as compared to the 1・2/W TPTD group. Trabecular BMD values in the FS and TH were significantly increased in the 1/D TPTD group, as compared to the 1・2/W TPTD group, while the cortical BMD values in the TR, FS, and TH were significantly increased in the 1・2/W TPTD group, as compared to the 1/D TPTD group. CONCLUSION: Trends toward more favorable improvement of the cortical bone by 1・2/W TPTD and that of the trabecular bones by 1/D TPTD were observed.

Asunto(s)

Absorciometría de Fotón , Conservadores de la Densidad Ósea , Densidad Ósea , Fémur , Imagenología Tridimensional , Teriparatido , Humanos , Teriparatido/administración & dosificación , Teriparatido/farmacología , Femenino , Densidad Ósea/efectos de los fármacos , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Masculino , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/farmacología , Fémur/efectos de los fármacos , Fémur/diagnóstico por imagen , Imagenología Tridimensional/métodos , Osteoporosis/tratamiento farmacológico , Osteoporosis/diagnóstico por imagen , Esquema de Medicación , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga

RESUMEN

Biomaterial-based approaches for bone regeneration seek to explore alternative strategies to repair non-healing fractures and critical-sized bone defects. Fracture non-union occurs due to a number of factors resulting in the formation of bone defects. Rigorous evaluation of the biomaterials in relevant models and assessment of their potential to translate towards clinical use is vital. Large animal experimentation can be used to model fracture non-union while scaling-up materials for clinical use. Growth factors modulate cell phenotype, behaviour and initiate signalling pathways leading to changes in matrix deposition and tissue formation. Bone morphogenetic protein-2 (BMP-2) is a potent osteogenic growth factor, with a rapid clearance time in vivo necessitating clinical use at a high dose, with potential deleterious side-effects. The current studies have examined the potential for Laponite® nanoclay coated poly(caprolactone) trimethacrylate (PCL-TMA900) scaffolds to bind BMP-2 for enhanced osteoinduction in a large animal critical-sized bone defect. An ovine femoral condyle defect model confirmed PCL-TMA900 scaffolds coated with Laponite®/BMP-2 produced significant bone formation compared to the uncoated PCL-TMA 900 scaffold in vivo, assessed by micro-computed tomography (µCT) and histology. This indicated the ability of Laponite® to deliver the bioactive BMP-2 on the PCL-TMA900 scaffold. Bone formed around the Laponite®/BMP-2 coated PCL-TMA900 scaffold, with no erroneous bone formation observed away from the scaffold material confirming localisation of BMP-2 delivery. The current studies demonstrate the ability of a nanoclay to localise and deliver bioactive BMP-2 within a tailored octet-truss scaffold for efficacious bone defect repair in a large animal model with significant implications for translation to the clinic.

Asunto(s)

Proteína Morfogenética Ósea 2 , Regeneración Ósea , Fémur , Impresión Tridimensional , Silicatos , Andamios del Tejido , Animales , Proteína Morfogenética Ósea 2/administración & dosificación , Proteína Morfogenética Ósea 2/farmacología , Regeneración Ósea/efectos de los fármacos , Silicatos/química , Silicatos/farmacología , Silicatos/administración & dosificación , Andamios del Tejido/química , Ovinos , Fémur/patología , Fémur/lesiones , Fémur/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Osteogénesis/efectos de los fármacos , Modelos Animales de Enfermedad

RESUMEN

Background and Objectives: This study aimed to evaluate the histological and biochemical effects of capsaicin on implant osseointegration and oxidative stress. Materials and Methods: Male Wistar albino rats weighing between 250 and 300 g were used in this study. Twenty-four rats were randomly divided into three equal groups: implant + control (n = 8), implant + capsaicin-1 (n = 8), and implant + capsaicin-2 (n = 8). Additionally, 2.5 mm diameter and 4 mm length titanium implants were surgically integrated into the corticocancellous bone parts of the femurs. In the treatment groups, rats were injected intraperitoneally with 25 mg/kg (implant + capsaicin-1) and 50 mg/kg (implant + capsaicin-2) of capsaicin. No additional applications were made in the control group. Three rats in total died during and after the experiment as a result of the analyses performed on 21 animals. Results: The highest total antioxidant status value was found in capsaicin dose 2, according to the analysis. The control group had the highest total oxidant status and oxidative stress index values, while group 2 of capsaicin had the lowest. After analysis, we found that there was no observed positive effect on osteointegration in this study (p > 0.05), although the bone implant connection was higher in the groups treated with capsaicin. Conclusions: A positive effect on osteointegration was not observed in this study. This may be due to osteoclast activation. However, it was found that it has a positive effect on oxidative stress. Osteoclast activation may be the cause of this phenomenon. Capsaicin was found to have a positive effect on oxidative stress (p < 0.05). It was also observed to have a positive effect on oxidative stress.

Asunto(s)

Capsaicina , Oseointegración , Estrés Oxidativo , Ratas Wistar , Titanio , Animales , Capsaicina/farmacología , Capsaicina/administración & dosificación , Oseointegración/efectos de los fármacos , Masculino , Ratas , Estrés Oxidativo/efectos de los fármacos , Fémur/efectos de los fármacos , Fémur/cirugía , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/administración & dosificación , Distribución Aleatoria

RESUMEN

OBJECTIVES: This study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the murine femora, and whether the PTH-driven bone formation would facilitate osteoblastic differentiation into osteocytes. METHODS: Six-week-old male C57BL/6J mice were employed to examine the distribution of alkaline phosphatase (ALP), PHOSPHO1, podoplanin, and calcein labeling in two distinct long bone regions: the metaphyseal trabeculae close to the chondro-osseous junction (COJ) and those distant from the COJ in three mouse groups, a control group receiving a vehicle (sham group) and groups receiving hPTH (1-34) twice a day (PTH BID group) or four times a day (PTH QID group) for two weeks. RESULTS: The sham group showed PHOSPHO1-reactive mature osteoblasts localized primarily at the COJ, whereas the PTH BID/QID groups exhibited extended lines of PHOSPHO1-reactive osteoblasts even in regions distant from the COJ. The PTH QID group displayed fragmented calcein labeling in trabeculae close to the COJ, whereas continuous labeling was observed in trabeculae distant from the COJ. Osteoblasts tended to express podoplanin and PHOSPHO1 independently in the close and distant regions of the sham group, while osteoblasts in the PTH-administered groups showed immunoreactivity of podoplanin and PHOSPHO1 together in the close and distant regions. CONCLUSIONS: Administration of PTH may accelerate remodeling-based bone formation in regions close to the COJ while predominantly inducing modeling-based bone formation in distant regions. PTH appeared to simultaneously facilitate osteoblastic bone mineralization and differentiation into osteocytes in both remodeling- and modeling-based bone formation.

Asunto(s)

Fosfatasa Alcalina , Fémur , Fluoresceínas , Ratones Endogámicos C57BL , Osteoblastos , Hormona Paratiroidea , Animales , Fosfatasa Alcalina/metabolismo , Ratones , Masculino , Fémur/efectos de los fármacos , Fémur/metabolismo , Hormona Paratiroidea/metabolismo , Hormona Paratiroidea/farmacología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Glicoproteínas de Membrana/metabolismo , Remodelación Ósea/efectos de los fármacos , Osteocitos/metabolismo , Osteocitos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Monoéster Fosfórico Hidrolasas

RESUMEN

BACKGROUND: As a two-stage surgical procedure, Masquelet's technique has been used to care for critical-size bone defects (CSD). We aimed to determine the effects of modified and altered bone cement with biological or chemical enriching agents on the progression of Masquelet's induced membrane (IM) applied to a rat femur CSD model, and to compare the histopathological, biochemical, and immunohistochemical findings of these cements to enhance IM capacity. METHODS: Thirty-five male rats were included in five groups: plain polymethyl methacrylate (PMMA), estrogen-impregnated PMMA (E+PMMA), bone chip added PMMA (BC+PMMA), hydroxyapatite-coated PMMA (HA) and calcium phosphate cement (CPC). The levels of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) were analyzed in intracardiac blood samples collected at the end of 4 weeks of the right femur CSD intervention. All IMs collected were fixed and prepared for histopathological scoring. The tissue levels of rat-specific Transforming Growth Factor-Beta (TGF-ß), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) were analyzed immunohistochemically. RESULTS: Serum levels of BALP and OC were significantly higher in E+PMMA and BC+PMMA groups than those of other groups (P = 0.0061 and 0.0019, respectively). In contrast, TNF-α levels of all groups with alternative bone cement significantly decreased compared to bare PMMA (P = 0.0116). Histopathological scores of E+PMMA, BC+PMMA, and CPC groups were 6.86 ± 1.57, 4.71 ± 0.76, and 6.57 ± 1.51, respectively, which were considerably higher than those of PMMA and HA groups (3.14 ± 0.70 and 1.86 ± 0.69, respectively) (P < 0.0001). Significant increases in TGF-ß and VEGF expressions were observed in E+PMMA and CPC groups (P = 0.0001 and <0.0001, respectively) whereas Runx2 expression significantly increased only in the HA group compared to other groups (P < 0.0001). CONCLUSIONS: The modified PMMA with E and BC, and CPC as an alternative spacer resulted in a well-differentiated IM and increased IM progression by elevating BALP and OC levels in serum and by mediating expressions of TGF-ß and VEGF at the tissue level. Estrogen-supplemented cement spacer has yielded promising findings between modified and alternative bone cement.

Asunto(s)

Cementos para Huesos , Modelos Animales de Enfermedad , Fémur , Polimetil Metacrilato , Factor A de Crecimiento Endotelial Vascular , Animales , Ratas , Masculino , Factor A de Crecimiento Endotelial Vascular/metabolismo , Fémur/patología , Fémur/efectos de los fármacos , Fracturas del Fémur/patología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Osteocalcina/metabolismo , Fosfatasa Alcalina/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ratas Sprague-Dawley , Fosfatos de Calcio , Curación de Fractura/efectos de los fármacos , Curación de Fractura/fisiología , Regeneración Ósea/efectos de los fármacos , Durapatita

RESUMEN

BACKGROUND AND OBJECTIVES: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model. METHODS: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed. RESULTS: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively). CONCLUSION: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

Asunto(s)

Fracturas del Fémur , Curación de Fractura , Ratas Wistar , Ácido Vanílico , Animales , Ácido Vanílico/farmacología , Ácido Vanílico/uso terapéutico , Curación de Fractura/efectos de los fármacos , Masculino , Fracturas del Fémur/tratamiento farmacológico , Fracturas del Fémur/patología , Ratas , Modelos Animales de Enfermedad , Fenómenos Biomecánicos/efectos de los fármacos , Fémur/efectos de los fármacos , Fémur/patología , Callo Óseo/efectos de los fármacos , Callo Óseo/patología

RESUMEN

Introduction: The ongoing concern of the medical profession regarding chronic medication is related to increasing patient adherence and compliance to treatment and reducing medication side effects. In this respect, drugs represented by fixed-dose combinations of active substances within the same tablet have emerged. Such a principle can be extrapolated by following the potential beneficial effects that a chronic medication can have on chronic pathologies affecting different systems. Materials and Methods: The study included 48 female Albino Wistar rats, aged 16-18 months, which were divided into two groups: ovariectomized and non-ovariectomized rats. One batch of 12 non-ovariectomized rats received no treatment, becoming a control batch (NOVX-M). The ovariectomized (OVX) group was divided into 3 batches of 12 rats each: no treatment, control (OVX-M), fenofibrate-treated (OVX-F) and statin-treated (OVX-S) rats. At 12 weeks after ovariectomy, a femoral fracture occurred in the right hind limb of all animals included in the experiment To reveal the changes, at intervals of 2, 4, 6 and 8 weeks post-fracture, the proximal part of the femur was evaluated by NMR diffusiometry, which allows random motion of proton molecules expressed by self-diffusion coefficients, D, thus allowing analysis of the size and complexity of microscopic order cavities within biological structures, such as pores inside bones. Results: The effects of hypolipidemic medication in the absence of estrogen were evidenced, proving the beneficial effect that fenofibrate can have in preserving healthy tissue exposed to osteoporotic risk during the menopausal period. The effects of lipid-lowering medication are also influenced by the duration of administration. Conclusions: Osteoporosis and heart disease are two chronic pathologies that affect mainly female population in the second half of life, and proving the dual therapeutic potential of lipid-lowering medication may also have positive effects by increasing adherence and compliance to treatment.

Asunto(s)

Hipolipemiantes , Ovariectomía , Ratas Wistar , Animales , Femenino , Ratas , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Hipolipemiantes/administración & dosificación , Espectroscopía de Resonancia Magnética/métodos , Fenofibrato/farmacología , Fenofibrato/uso terapéutico , Modelos Animales de Enfermedad , Fémur/efectos de los fármacos , Huesos/efectos de los fármacos

RESUMEN

Osteoporosis is characterized by bone loss and deterioration in bone microstructure, leading to bone fragility. It is strongly correlated with menopause in women. Previously, we reported that diets supplemented with a kudzu (Pueraria lobata) vine extract suppressed bone resorption in ovariectomized (OVX) mice, a postmenopausal model. The main isoflavone in kudzu is puerarin (daidzein-8-C-glycoside). Puerarin (daidzein-8-C-glycoside), which is main isoflavone of kudzu, probably contributes to the beneficial effect. However, the underlying mechanism is unclear. Therefore, the nutrikinetics of puerarin and the comparison with the suppressive effects of kudzu isoflavones on osteoclast differentiation was examined in this study. We demonstrated that orally administered puerarin was absorbed from the gut and entered the circulation in an intact form. In addition, puerarin accumulated in RAW264.7 pre-osteoclast cells in a time-dependent manner. Tartrate-resistant acid phosphatase activity was decreased by puerarin treatment in a concentration-dependent manner in RAW264.7 cells stimulated with the receptor activator of nuclear factor kappa-B ligand. Ovariectomy-induced elevated bone resorption was suppressed, and the fragile bone strength was improved by puerarin ingestion in the diet. These findings suggested that orally administered puerarin was localized in bone tissue and suppressed bone resorption and osteoclastogenesis in ovariectomized mice.

Asunto(s)

Diferenciación Celular , Fémur , Isoflavonas , Osteoclastos , Ovariectomía , Pueraria , Animales , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Osteoclastos/efectos de los fármacos , Femenino , Ratones , Fémur/efectos de los fármacos , Fémur/metabolismo , Pueraria/química , Diferenciación Celular/efectos de los fármacos , Células RAW 264.7 , Resorción Ósea/prevención & control , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Osteoporosis/prevención & control , Osteoporosis/tratamiento farmacológico , Fosfatasa Ácida Tartratorresistente/metabolismo

RESUMEN

Osteomyelitis is an invasive bone infection that can lead to severe pain and even disability, posing a challenge for orthopedic surgery. Naringin can reduce bone-related inflammatory conditions. This study aimed to elucidate the function and mechanism of naringin in a Staphylococcus aureus-induced mouse model of osteomyelitis. Femurs of S. aureus-infected mice were collected after naringin administration and subjected to microcomputed tomography to analyze cortical bone destruction and bone loss. Bacterial growth in femurs was also assessed. Proinflammatory cytokine levels in mouse femurs were measured using enzyme-linked immunosorbent assays. Pathological changes and bone resorption were analyzed using hematoxylin and eosin staining and tartrate-resistant acid phosphatase staining, respectively. Quantitative reverse transcription polymerase chain reaction and western blot analysis were used to quantify the messenger RNA and protein expression of osteogenic differentiation-associated genes in the femurs. The viability of human bone marrow-derived stem cells (hBMSCs) was determined using cell counting kit-8. Alizarin Red S staining and alkaline phosphatase staining were performed to assess the formation of mineralization nodules and bone formation in vitro. Notch signaling-related protein levels in femur tissues and hBMSCs were assessed using western blot analysis. Experimental results revealed that naringin alleviated S. aureus-induced cortical bone destruction and bone loss in mice by increasing the bone volume/total volume ratio. Naringin suppressed S. aureus-induced bacterial growth and inflammation in femurs. Moreover, it alleviated histopathological changes, inhibited bone resorption, and increased the expression of osteogenic markers in osteomyelitic mice. It increased the viability of hBMSCs and promoted their differentiation and bone mineralization in vitro. Furthermore, naringin activated Notch signaling by upregulating the protein levels of Notch1, Jagged1, and Hes1 in the femurs of model mice and S. aureus-stimulated hBMSCs. In conclusion, naringin reduces bacterial growth, inflammation, and bone resorption while upregulating the expression of osteogenic markers in S. aureus-infected mice and hBMSCs by activating Notch signaling.

Asunto(s)

Antibacterianos , Antiinflamatorios , Flavanonas , Osteomielitis , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Flavanonas/farmacología , Ratones , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Osteomielitis/metabolismo , Osteomielitis/patología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Humanos , Masculino , Osteogénesis/efectos de los fármacos , Fémur/patología , Fémur/metabolismo , Fémur/microbiología , Fémur/efectos de los fármacos

RESUMEN

BACKGROUND/AIM: This study aimed to investigate the structure and functions of the membrane formed around liquid nitrogen-treated bones in the osteogenesis and revitalization of frozen bone using a rat model. MATERIALS AND METHODS: Segmental defects were created in femurs of rats, and resected bones treated with liquid nitrogen [frozen bone (FB) group, n=20] or polymethylmethacrylate (PMMA group; n=20) were implanted as spacers. Histological analysis and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) of the membrane around each spacer were performed for bone morphogenetic protein 2 (BMP2), transforming growth factor (TGF)-ß1, and vascular endothelial growth factor (VEGF). Furthermore, in week 2, spacers were removed from both groups (n=5 each), and autologous cancellous bone (ACB) harvested from the ilium was grafted into the defect. Radiological analysis was performed until bone union was observed. RESULTS: In week 2, similar two-layered membrane structures were observed in both groups; these matured into fibrous tissues over time. At each evaluation point, qRT-PCR showed higher expression of all factors in the FB than in the PMMA group. In the ACB graft model, the mean period to bone union and new bone volume were significantly shorter and greater, respectively, in the FB. Chondrocytes invaded the osteotomy site from the membrane in the FB, suggesting that endochondral ossification may occur and be related to osteogenesis. Additionally, fibroblasts and capillaries in the membrane invaded the surface of treated bone in week 2, and osteocytes were observed around them in weeks 6 and 8. CONCLUSION: Fibrous membranous tissue formed around liquid nitrogen-treated bones may be vital for osteogenesis and revitalization of frozen bones.

Asunto(s)

Osteogénesis , Factor A de Crecimiento Endotelial Vascular , Animales , Osteogénesis/efectos de los fármacos , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Nitrógeno/metabolismo , Proteína Morfogenética Ósea 2/metabolismo , Proteína Morfogenética Ósea 2/genética , Masculino , Trasplante Óseo/métodos , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Polimetil Metacrilato/farmacología , Fémur/efectos de los fármacos , Fémur/metabolismo , Fémur/patología , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/patología , Ratas Sprague-Dawley

RESUMEN

Osteoporosis is a major public health problem with an urgent need for safe and effective therapeutic interventions. The process of shell formation in oysters is similar to that of bone formation in mammals, and oyster extracts have been proven to exert osteoprotective effects. Oyster mantle is the most crucial organ regulating shell formation, in which exosomes play an important role. However, the effects of oyster mantle-derived exosomes (OMEs) on mammalian osteoporosis and the underlying mechanisms remain unknown. The OMEs investigated herein was found to carry abundant osteogenic cargos. They could also survive hostile gastrointestinal conditions and accumulate in the bones following oral administration. Moreover, they promoted osteoblastic differentiation and inhibited osteoclastic differentiation simultaneously. Further mechanistic examination revealed that OMEs likely promoted osteogenic activity by activating PI3K/Akt/ß-catenin pathway in osteoblasts and blunted osteoclastic activity by inhibiting NF-κB pathway in osteoclasts. These favorable pro-osteogenic effects of OMEs were also corroborated in a rat femur defect model. Importantly, oral administration of OMEs effectively attenuated bone loss and improved the bone microstructure in ovariectomy-induced osteoporotic mice, and demonstrating excellent biosafety. The mechanistic insights from our data support that OMEs possess promising therapeutic potential against osteoporosis.

Asunto(s)

Exosomas , Homeostasis , Osteoblastos , Osteogénesis , Osteoporosis , Ostreidae , Animales , Exosomas/metabolismo , Osteoporosis/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/patología , Osteogénesis/efectos de los fármacos , Femenino , Ratones , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Homeostasis/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Diferenciación Celular/efectos de los fármacos , Ratas Sprague-Dawley , Huesos/efectos de los fármacos , Huesos/metabolismo , Huesos/patología , Exoesqueleto/química , Ratas , Ratones Endogámicos C57BL , Células RAW 264.7 , Ovariectomía , Fémur/efectos de los fármacos , Fémur/patología , Fémur/metabolismo

RESUMEN

BACKGROUND: Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem. METHODS: This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone. RESULTS: Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18. CONCLUSIONS: Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Asunto(s)

Absorciometría de Fotón , Artroplastia de Reemplazo de Cadera , Conservadores de la Densidad Ósea , Densidad Ósea , Fémur , Osteoporosis Posmenopáusica , Proteína Relacionada con la Hormona Paratiroidea , Humanos , Femenino , Proteína Relacionada con la Hormona Paratiroidea/farmacología , Proteína Relacionada con la Hormona Paratiroidea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/farmacología , Osteoporosis Posmenopáusica/tratamiento farmacológico , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Persona de Mediana Edad , Fémur/efectos de los fármacos , Fémur/diagnóstico por imagen , Fémur/cirugía

RESUMEN

This investigation aimed to construct a bilayer scaffold integrating alginate and gelatin with nanobioactive glass (BG), recognized for their efficacy in tissue regeneration and drug delivery. Scaffolds, namely, alginate/gelatin (AG), alginate-/actonel gelatin (AGD), alginate actenol/gelatin-45S5 BG (4AGD), and alginate-actonel/gelatin-59S BG (5AGD), were assembled using a cost-effective freeze-drying method, followed by detailed structural investigation via powder X-ray diffraction as well as morphological characterization using field emission scanning electron microscopy (FESEM). FESEM revealed a honeycomb-like morphology with distinct pore sizes for nutrient, oxygen, and drug transport. The scaffolds evidently exhibited hemocompatibility, high porosity, good swelling capacity, and biodegradability. In vitro studies demonstrated sustained drug release, particularly for scaffolds containing actonel. In vivo tests showed that the bilayer scaffold promoted new bone formation, surpassing the control group in bone area increase. The interaction of the scaffold with collagen and released ions improved the osteoblastic function and bone volume fraction. The findings suggest that this bilayer scaffold could be beneficial for treating critical-sized bone defects, especially in the mandibular and femoral regions.

Asunto(s)

Fémur , Vidrio , Mandíbula , Andamios del Tejido , Andamios del Tejido/química , Animales , Vidrio/química , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Mandíbula/efectos de los fármacos , Fémur/efectos de los fármacos , Fémur/diagnóstico por imagen , Fémur/patología , Gelatina/química , Regeneración Ósea/efectos de los fármacos , Alginatos/química , Porosidad , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos