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1.
Life Sci ; 241: 117132, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837327

RESUMO

INTRODUCTION: This study aimed to verify the effects of cigarette smoke exposure in bone mineralization and fibrillar matrix composition as well as in bone healing after tibial fracture induction. METHODS: C57Bl/6 Mice were assigned according to exposure and surgery: C room air; F room air and tibia open osteotomy; CS cigarette smoke; FCS cigarette smoke and tibia open osteotomy. In order to study fracture healing we performed, under anesthesia, a bone injury through a tibial shaft osteotomy. Bone samples were obtained to evaluate bone histomorphometry, trabecular morphology and volume, trabecular collagen types composition and presence of inflammatory cytokines and growth factors. RESULTS: CS exposure significantly reduced the thickness of bone trabeculae associated with decrease in mineralizing surface and mineral deposition rate, leading a lower bone formation rate and longer mineralization time. Resorption surface and osteoclastic surface were greater in the CS group, attesting increased resorptive action. There was a decrease in type I collagen deposition and genes expression in the CS and FCS groups compared to C group and in contrast there was an increase in type V collagen deposition and genes expression in the CS, FC and FSC groups compared to C group. Also, CS exposure induced a decrease in bone forming cytokines and an increase in inflammatory associated cytokines, and these changes were intensified under fracture conditions. CONCLUSION: Cigarette smoke exposure alters bone matrix composition and worsens bone mineralization, leading to bone fragility by increasing collagen V synthesis and deposition and impairing collagen I fibril forming and assembling. And these deleterious effects contributed to the worsening in fracture healing after tibia osteotomy.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Osteogênese/efeitos dos fármacos , Fumaça/efeitos adversos , Tíbia/patologia , Fraturas da Tíbia/patologia , Animais , Colágeno Tipo I/metabolismo , Citocinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tíbia/efeitos dos fármacos , Tíbia/lesões , Tíbia/metabolismo , Fraturas da Tíbia/etiologia , Fraturas da Tíbia/metabolismo
2.
Toxicol Lett ; 321: 122-130, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31874197

RESUMO

Our previous studies confirmed that prenatal caffeine exposure (PCE) could induce susceptibility to osteoarthritis in adult offspring rats due to poor chondrocyte differentiation, but its mechanism remains to be further investigated. This study aimed to explore whether subchondral bone dysplasia mediates susceptibility to osteoarthritis in adult offspring rats induced by PCE. Pregnant Wistar rats were treated with caffeine (120 mg/kg.d) or saline from gestational day (GD) 9 to 20. The female offspring were euthanized to collect femurs at GD20, postnatal week (PW) 6, and PW28 (non-ovariectomy and ovariectomy groups) to detect osteoarthritis-like phenotype, subchondral bone mass, ossification center development, and other evidence. The results showed that PCE increased the Mankin score of pathological articular cartilage, but decreased articular cartilage thickness and subchondral bone mass, which were more obvious after ovariectomy. Meanwhile, the correlation analysis results demonstrated that the Mankin score of articular cartilage was significantly negatively correlated with subchondral bone mass, and the thickness of articular cartilage was significantly positively correlated with subchondral bone mass. Further, the length and area of the primary and secondary ossification centers, the number of osteoblasts, and the related genes' expression of osteogenic differentiation (e.g., Runx2, BSP, ALP, and OCN) were all significantly decreased in the PCE group before and after birth. Taken together, PCE induced susceptibility to osteoarthritis in adult female offspring, which was likely related to the subchondral bone dysplasia and reduction of subchondral bone mass production due to developmental disorder of primary and secondary ossification centers caused by osteoblast differentiation disability before and after birth.


Assuntos
Doenças do Desenvolvimento Ósseo/induzido quimicamente , Cafeína/toxicidade , Cartilagem Articular/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/toxicidade , Osteoartrite/induzido quimicamente , Osteogênese/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Fatores Etários , Animais , Doenças do Desenvolvimento Ósseo/genética , Doenças do Desenvolvimento Ósseo/metabolismo , Doenças do Desenvolvimento Ósseo/patologia , Cartilagem Articular/patologia , Diferenciação Celular/efeitos dos fármacos , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Fêmur/patologia , Idade Gestacional , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteogênese/genética , Ovariectomia , Gravidez , Ratos Wistar , Fatores Sexuais , Tíbia/efeitos dos fármacos , Tíbia/metabolismo , Tíbia/patologia
3.
PLoS Genet ; 15(12): e1008530, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31841498

RESUMO

Vitamin D is important for normal skeletal homeostasis, especially in growing children. There are no previous genome-wide association (GWA) studies exploring genetic factors that influence vitamin D metabolism in early childhood. We performed a GWA study on serum 25-hydroxyvitamin D (25(OH)D) and response to supplementation in 761 healthy term-born Finnish 24-month-old children, who participated in a randomized clinical trial comparing effects of 10 µg and 30 µg of daily vitamin D supplementation from age 2 weeks to 24 months. Using the Illumina Infinium Global Screening Array, which has been optimized for imputation, a total of 686085 markers were genotyped across the genome. Serum 25(OH)D was measured at the end of the intervention at 24 months of age. Skeletal parameters reflecting bone strength were determined at the distal tibia at 24 months using peripheral quantitative computed tomography (pQCT) (data available for 648 children). For 25(OH)D, two strong GWA signals were identified, localizing to GC (Vitamin D binding protein) and CYP2R1 (Vitamin D 25-hydroxylase) genes. The GWA locus comprising the GC gene also associated with response to supplementation. Further evidence for the importance of these two genes was obtained by comparing association signals to gene expression data from the Genotype-Tissue Expression project and performing colocalization analyses. Through the identification of haplotypes associated with low or high 25(OH)D concentrations we used a Mendelian randomization approach to show that haplotypes associating with low 25(OH)D were also associated with low pQCT parameters in the 24-month-old children. In this first GWA study on 25(OH)D in this age group we show that already at the age of 24 months genetic variation influences 25(OH)D concentrations and determines response to supplementation, with genome-wide significant associations with GC and CYP2R1. Also, the dual association between haplotypes, 25(OH)D and pQCT parameters gives support for vertical pleiotropy mediated by 25(OH)D.


Assuntos
Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Tíbia/diagnóstico por imagem , Proteína de Ligação a Vitamina D/genética , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Desenvolvimento Infantil , Pré-Escolar , Feminino , Finlândia , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Masculino , Análise da Randomização Mendeliana , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Ensaios Clínicos Controlados Aleatórios como Assunto , Tíbia/efeitos dos fármacos , Tíbia/crescimento & desenvolvimento , Tomografia Computadorizada por Raios X , Vitamina D/sangue , Vitamina D/farmacocinética
4.
Environ Sci Pollut Res Int ; 26(36): 36322-36332, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31713825

RESUMO

The widespread use of thiram has raised concerns for health and its toxic effects, but the underlying toxicity mechanism on platelets and bones is poorly defined. Here, we found a significant increase in the number of platelets in chickens with the thiram intake, due to the increased expression of thrombopoietin mRNA in the dysfunction liver. Furthermore, the decreased vascular distribution and cell death of chondrocytes in the tibial growth plates (TGPs) were observed, resulting in bone growth inhibition, which is associated with the abnormal activation of platelets leading to the extraordinary decrease of vascular endothelial growth factor A (VEGFA) and angiopoietin-1 protein were released and their corresponding receptors VEGFR2 and Tie-2 expressions were also reduced in the TGPs. Taken together, these findings revealed that thiram has an adverse effect on bones and platelets, which may have a high risk of thrombosis and osteoarthritis.


Assuntos
Galinhas/sangue , Galinhas/crescimento & desenvolvimento , Lâmina de Crescimento/efeitos dos fármacos , Praguicidas/toxicidade , Tiram/toxicidade , Proteínas Angiogênicas/metabolismo , Animais , Lâmina de Crescimento/irrigação sanguínea , Lâmina de Crescimento/metabolismo , Lâmina de Crescimento/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Contagem de Plaquetas , Trombopoetina/metabolismo , Tíbia/efeitos dos fármacos , Tíbia/crescimento & desenvolvimento
5.
Nat Commun ; 10(1): 4533, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586071

RESUMO

Multiple myeloma is an incurable, bone marrow-dwelling malignancy that disrupts bone homeostasis causing skeletal damage and pain. Mechanisms underlying myeloma-induced bone destruction are poorly understood and current therapies do not restore lost bone mass. Using transcriptomic profiling of isolated bone lining cell subtypes from a murine myeloma model, we find that bone morphogenetic protein (BMP) signalling is upregulated in stromal progenitor cells. BMP signalling has not previously been reported to be dysregulated in myeloma bone disease. Inhibition of BMP signalling in vivo using either a small molecule BMP receptor antagonist or a solubilized BMPR1a-FC receptor ligand trap prevents trabecular and cortical bone volume loss caused by myeloma, without increasing tumour burden. BMP inhibition directly reduces osteoclastogenesis, increases osteoblasts and bone formation, and suppresses bone marrow sclerostin levels. In summary we describe a novel role for the BMP pathway in myeloma-induced bone disease that can be therapeutically targeted.


Assuntos
Doenças Ósseas/tratamento farmacológico , Proteínas Morfogenéticas Ósseas/metabolismo , Mieloma Múltiplo/complicações , Pirazóis/farmacologia , Pirimidinas/farmacologia , Células-Tronco/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Medula Óssea/patologia , Receptores de Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Receptores de Proteínas Morfogenéticas Ósseas/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Fêmur/citologia , Fêmur/efeitos dos fármacos , Fêmur/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos , Mieloma Múltiplo/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/patologia , Tíbia/citologia , Tíbia/efeitos dos fármacos , Tíbia/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Artigo em Inglês | MEDLINE | ID: mdl-31505801

RESUMO

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.


Assuntos
Síndrome Metabólica/metabolismo , Osteoporose/metabolismo , Tíbia/efeitos dos fármacos , Tocotrienóis/farmacologia , Animais , Bixaceae , Proteínas Morfogenéticas Ósseas/metabolismo , Carotenoides , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/metabolismo , Marcadores Genéticos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Síndrome Metabólica/complicações , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Osteoporose/etiologia , Osteoprotegerina/metabolismo , Hormônio Paratireóideo/metabolismo , Extratos Vegetais , Ligante RANK/metabolismo , Ratos Wistar , Tíbia/metabolismo
7.
Arch Anim Nutr ; 73(6): 445-456, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31553227

RESUMO

To investigate effects of dietary calcium (Ca) and phosphorus (P) levels and 25-hydroxycholecalciferol (25OHD3) supplementation on performance and bone properties of broiler starters, 224 male Arbor Acre broilers were used in a 21-d trial. Broilers were allotted to one of four treatments in a 2 × 2 factorial arrangement including diets either normal or low in Ca and P, which were further supplemented or not with 69 µg 25OHD3/kg feed. Feeding low Ca and P diets significantly reduced performance of boilers and decreased ash, Ca, P and hydroxyproline contents in tibias and femurs (p < 0.05). Ultimate load, bending moment, stiffness and energy to fail were decreased (p < 0.05) in broilers fed diets deficient in Ca and P. Addition of 25OHD3 did not influence performance but significantly increased serum 25OHD3 levels. Furthermore, the addition of 25OHD3 caused an increased tibial and femoral bone density and femoral hydroxyproline content (p < 0.05), increased bending moment in tibias (p < 0.05), and enhanced ultimate load and bending moment in femurs (p < 0.05). No significant interactions were observed for bone properties. Overall, feeding 25OHD3 at 69 µg/kg feed to broilers had no effect on growth performance but partly improved bone biochemical and biomechanical properties of broiler starters.


Assuntos
Cálcio na Dieta/metabolismo , Galinhas/fisiologia , Fêmur/efeitos dos fármacos , Hidroxicolecalciferóis/metabolismo , Fósforo na Dieta/metabolismo , Tíbia/fisiologia , Ração Animal/análise , Animais , Fenômenos Biomecânicos , Galinhas/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Fêmur/fisiologia , Hidroxicolecalciferóis/administração & dosagem , Masculino , Distribuição Aleatória , Tíbia/efeitos dos fármacos
8.
Bone Joint J ; 101-B(7_Supple_C): 108-114, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31256654

RESUMO

AIMS: It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway. MATERIALS AND METHODS: An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31hiEMCNhi endothelium. RNA sequencing analysis was performed using sorted CD31hiEMCNhi endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells. RESULTS: Flow cytometry revealed that anti-VEGFR treatment decreased CD31hiEMCNhi vascular endothelium in the peri-implant bone versus controls at two weeks post-implantation. This was confirmed by the decrease of CD31 and endomucin (EMCN) double-positive cells detected with immunofluorescence. In addition, treated mice had more OPN-positive cells in both peri-implant bone and tissue on the implant surface at two weeks and four weeks, respectively. More OSX-positive cells were present in peri-implant bone at two weeks. More importantly, anti-VEGFR treatment decreased the maximum load of pull-out testing compared with the control. CONCLUSION: VEGF pathway controls the coupling of angiogenesis and osteogenesis in orthopaedic implant osseointegration by affecting the formation of CD31hiEMCNhi endothelium. Cite this article: Bone Joint J 2019;101-B(7 Supple C):108-114.


Assuntos
Inibidores da Angiogênese/farmacologia , Interface Osso-Implante/patologia , Osseointegração/efeitos dos fármacos , Próteses e Implantes , Tíbia/cirurgia , Titânio , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Tíbia/efeitos dos fármacos , Tíbia/metabolismo , Tíbia/patologia
9.
PLoS One ; 14(7): e0219575, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291372

RESUMO

Parathyroid hormone (PTH) is an anabolic bone drug approved by the US Food and Drug Administration (FDA) to treat osteoporosis. However, previous studies using cross-sectional designs have reported variable and sometimes contradictory results. The aim of the present study was to quantify the localized effect of PTH on the structural and densitometric behaviors of mouse tibia and their links with the global mechanical behavior of bone using a novel spatiotemporal image analysis approach and a finite element analysis technique. Twelve female C57BL/6J mice were divided into two groups: the control and PTH treated groups. The entire right tibiae were imaged using an in vivo micro-computed tomography (µCT) system eight consecutive times. Next, the in vivo longitudinal tibial µCT images were rigidly registered and divided into 10 compartments across the entire tibial space. The bone volume (BV), bone mineral content (BMC), bone tissue mineral density (TMD), and tibial endosteal and periosteal areas (TEA and TPA) were quantified in each compartment. Additionally, finite element models of all the tibiae were generated to analyze the failure behavior of the tibia. It was found that both the BMC and BV started to increase in the proximal tibial region, and then the increases extended to the entire tibial region after two weeks of treatment (p < 0.05). PTH intervention significantly reduced the TEA in most tibial compartments after two weeks of treatment, and the TPA increased in most tibial regions after four weeks of treatment (p < 0.05). Tibial failure loads significantly increased after three weeks of PTH treatment (p < 0.01). The present study provided the first evidence of the localized effect of PTH on bone structural and densitometric properties, as well as their links with the global mechanical behaviors of bone, which are important pieces of information for unveiling the mechanism of PTH intervention.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Hormônio Paratireóideo/farmacologia , Tíbia/efeitos dos fármacos , Animais , Densitometria/métodos , Modelos Animais de Doenças , Feminino , Análise de Elementos Finitos , Camundongos , Camundongos Endogâmicos C57BL , Osteoporose/complicações , Fraturas por Osteoporose/etiologia , Hormônio Paratireóideo/uso terapêutico , Análise Espaço-Temporal , Tíbia/diagnóstico por imagem , Tíbia/fisiologia , Suporte de Carga , Microtomografia por Raio-X
10.
Int J Mol Sci ; 20(13)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261680

RESUMO

Chlorogenic acid (CGA) is a widely applied traditional Chinese medicine ingredient which can be used for the treatment of osteoporosis. In this experiment, we investigated the potential therapeutic effect of chlorogenic acid on thiram-induced tibial dyschondroplasia (TD) and explored the underlying mechanisms that have been rarely mentioned by others yet. Performance indicator analysis and tibial parameter analysis showed that CGA exhibited a definite positive effect on thiram-induced TD chickens. In order to further explore the mechanisms underlying the positive actions of CGA, apoptotic, autophagic genes and MMPs involved in matrix mineralization of growth plate were evaluated in this study. The results showed that CGA decreased the expression of pro-apoptotic genes caspases-3 and caspases-9, leading to the reduction of apoptotic cells accumulated in growth plate. In addition, CGA also increased the level of BECN1, an important gene involved in autophagy, which benefits the survival of abnormal cells. Furthermore, CGA also increased the expression of MMP-9, MMP-10, and MMP-13, which can directly affect the ossification of bones. Altogether, these results demonstrate that CGA possesses a positive therapeutic effect on thiram-induced TD via modulating the expression of caspases and BECN1 and regulating the degradation of ECM (extracellular matrix).


Assuntos
Proteína Beclina-1/metabolismo , Ácido Clorogênico/uso terapêutico , Matriz Extracelular/metabolismo , Osteocondrodisplasias/tratamento farmacológico , Animais , Apoptose , Autofagia , Proteína Beclina-1/genética , Caspases/genética , Caspases/metabolismo , Galinhas , Ácido Clorogênico/farmacologia , Matriz Extracelular/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Osteocondrodisplasias/etiologia , Tiram/toxicidade , Tíbia/efeitos dos fármacos , Tíbia/metabolismo , Tíbia/patologia
11.
Poult Sci ; 98(10): 4729-4744, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329980

RESUMO

In a 2 × 2 × 2 factorial design, the effects of dietary non-phytate phosphorus (NPP) levels, 0.17% (low) and 0.33% (moderate), diet moisture (dry and wet), and diet particle size (coarse and fine), were studied on egg production, characteristics of gastrointestinal tract (GIT) and tibia, digesta pH, and phytase activity in layer pullets (16 to 28 wk of age). The low NPP diet increased average daily water intake (ADWI) to ADFI ratio (4.2%) from 16 to 17 wk, but decreased this ratio (2.8%) from 23 to 27 wk. It decreased ADFI (1.5%) and egg mass production (3.8%) from 19 to 22 wk. It decreased egg weight (0.29 g) and ADWI (2.1%) from 23 to 27 wk. At 22 wk, the GIT relative empty organ weights were (g/kg BW) higher for proventriculus + gizzard (0.96), duodeneum (0.94), and jejunum + ileum (1.95) with the low vs. moderate NPP diet. The low NPP diet decreased digesta phytase activity in crop and proventriculus+gizzard at 28 wk. The wet diet increased ADFI, ADWI, and ADWI/ADFI ratio from 16 to 27 wk, egg mass production (3.0%) from 19 to 22 wk, and egg weight (0.45 g) from 23 to 27 wk. The wet diet also increased digesta phytase activity in proventriculus+gizzard. The coarse diet decreased ADFI from 19 to 22 wk (1.7%) and 23 to 27 wk (1.2%). The coarse diet caused reduced egg mass production (2.6%) from 23 to 27 wk. Egg shell breaking strength was increased on the coarse diet (0.9 Newton). The coarse diet increased ADWI/ADFI ratio from 16 to 27 wk, and increased relative gizzard weight by 1.95 and 0.81 g/kg BW at 22 and 28 wk, respectively. The coarse diet increased jejunal/ileal pH with 0.16 units at 28 wk. None of the tested parameters affected tibia characteristics. It was concluded that a low NPP diet did not clearly affect the studied parameters. The wet diet increased ADFI, ADWI, and egg production. The coarse diet increased ADWI, egg shell breaking strength, relative gizzard weight, and reduced ADFI and egg production.


Assuntos
6-Fitase/metabolismo , Galinhas/fisiologia , Trato Gastrointestinal/efeitos dos fármacos , Fósforo na Dieta/metabolismo , Fósforo/metabolismo , Tíbia/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta/veterinária , Fezes/química , Feminino , Trato Gastrointestinal/fisiologia , Fósforo na Dieta/administração & dosagem , Tíbia/fisiologia
12.
Biomed Pharmacother ; 118: 109207, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306971

RESUMO

A combination of diosmin and hesperidin (9:1 ratio) is marketed as a dietary supplement/nutraceutical for cardiovascular health. We studied the skeletal effect of this combination (90% diosmin and 10% hesperidin, henceforth named as DH). We showed that a) in rats with femur osteotomy, DH stimulated callus bone regeneration, b) in growing rats, DH promoted peak bone mass achievement and c) in OVX rats rendered osteopenic, DH completely restored femur trabecular bones and strength along with the increases in surface referent bone formation and serum osteogenic marker. Furthermore, DH suppressed bone resorption in OVX rats as well as in OVX rats treated with teriparatide (human parathyroid hormone 1-34) but did not affect the osteoanabolic effect of teriparatide. These data suggested that DH could prolong the anabolic window of teriparatide. To understand the mechanism of DH action, we performed pharmacokinetic studies and observed that upon its oral administration the only circulating metabolites was diosmetin (the aglycone form of diosmin) while none of the two input flavanones were detectable. Accordingly, subsequent experiments with diosmetin revealed that it was a selective estrogen receptor-ß agonist that stimulated osteoblast differentiation and suppressed sclerostin the anti-osteoblastogenic Wnt antagonist. Taken together, our study defined a positive skeletal effect of DH.


Assuntos
Doenças Ósseas Metabólicas/prevenção & controle , Regeneração Óssea/efeitos dos fármacos , Diosmina/farmacologia , Hesperidina/farmacologia , Osteogênese/efeitos dos fármacos , Teriparatida/farmacologia , Animais , Animais Recém-Nascidos , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/metabolismo , Suplementos Nutricionais , Diosmina/administração & dosagem , Feminino , Fêmur/efeitos dos fármacos , Fêmur/crescimento & desenvolvimento , Fêmur/metabolismo , Hesperidina/administração & dosagem , Ratos Sprague-Dawley , Teriparatida/administração & dosagem , Tíbia/efeitos dos fármacos , Tíbia/crescimento & desenvolvimento , Tíbia/metabolismo
13.
Nutrients ; 11(6)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234292

RESUMO

There is growing interest in bioactive substances from marine organisms for their potential use against diverse human diseases. Osteoporosis is a skeletal disorder associated with bone loss primarily occurring through enhanced osteoclast differentiation and resorption. Recently, we reported the anti-osteoclastogenic activity of fermented Pacific oyster (Crassostrea gigas) extract (FO) in vitro. The present study focused on investigating the anti-osteoporotic efficacy of FO in bone loss prevention in an experimental animal model of osteoporosis and elucidating the mechanism underlying its effects. Oral administration of FO significantly decreased ovariectomy-induced osteoclast formation and prevented bone loss, with reduced serum levels of bone turnover biomarkers including osteocalcin and C-terminal telopeptide fragment of type I collagen C-terminus (CTX). FO significantly suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts and attenuated the induction of osteoclast-specific genes required for osteoclastogenesis and bone resorption. Furthermore, FO inhibited RANKL-mediated IκBα and p65 phosphorylation in BMMs. Taken together, these results demonstrate that FO effectively suppresses osteoclastogenesis in vivo and in vitro, and that FO can be considered as a potential therapeutic option for the treatment of osteoporosis and osteoclast-mediated skeletal diseases.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Crassostrea/microbiologia , Fermentação , Lactobacillus brevis/fisiologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/prevenção & controle , Ovariectomia , Alimentos Marinhos/microbiologia , Tíbia/efeitos dos fármacos , Actinas/metabolismo , Animais , Conservadores da Densidade Óssea/isolamento & purificação , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/fisiopatologia , Transdução de Sinais , Tíbia/metabolismo , Tíbia/patologia , Tíbia/fisiopatologia
14.
Biomater Sci ; 7(9): 3614-3626, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31210206

RESUMO

Injectable scaffolds have attracted much attention because of their minimum surgical invasiveness. However, limited osteogenic induction property and low mechanical properties hampered their application in bone tissue engineering. CaCO3 microspheres, which possess osteoinductivity, rough surfaces and specific binding sites for BMP-2, were first fabricated; after BMP-2 uploading, microspheres were further entrapped in fibrin-glue hydrogel. CaCO3 microspheres were co-functionalized with casein and heparin. To obtain a high encapsulation of heparin and thus BMP-2 uploading, along with controlled release and simultaneous maintenance of the presence of vaterite which had osteogenic induction property, fabrication parameters were optimized and microspheres were characterized using XRD, FITR and SEM. The formed CaCO3 had a microsphere morphology of ∼1 µm. Both vaterite and calcite phases were present and the relative amount of calcite phase increased with the amount of heparin. Sample 25 mM_4-1Hep with the highest loading amount of heparin was selected as carrier for BMP-2 and BMP-2 loaded CaCO3 microspheres were further entrapped in fibrin-glue hydrogel (FC-B). For the as-prepared composite hydrogel, mechanical properties were characterized and the presence of CaCO3 significantly elevated the tensile strength; controlled release of BMP-2 was sustained until day 21. Based on ALP activity, alizarin red staining and RT-PCR, in vitro osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was found to be significantly enhanced under induction of FC-B. Rabbit tibia bone defect model was applied to evaluate its in vivo performance. After implantation for 4 weeks, presence of composite hydrogel was observed in defects. After 8 weeks, bone defects of FC-B group were nearly completely healed. Using the fact that autologous scaffolds can be derived based on fibrin-glue hydrogel, the well-designed BMP-2 loaded fibrin-glue composite hydrogel demonstrated good potential in bone tissue engineering.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Cálcio/farmacologia , Hidrogéis/química , Microesferas , Osteogênese/efeitos dos fármacos , Tíbia/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/química , Cálcio/química , Carbonato de Cálcio/síntese química , Carbonato de Cálcio/química , Diferenciação Celular , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Adesivo Tecidual de Fibrina/síntese química , Adesivo Tecidual de Fibrina/química , Hidrogéis/síntese química , Coelhos , Tíbia/patologia , Engenharia Tecidual
15.
Lasers Med Sci ; 34(6): 1081-1088, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154596

RESUMO

This study aimed to evaluate, through histomorphometric analysis, the bone repair process in the tibia of rats treated with zoledronic acid and submitted to 808-nm low-level laser therapy (LLLT) by using arsenide aluminum gallium laser. For this purpose, 20 rats were used and distributed according to treatment: group 1-saline administration; group 2-treated with LLLT; group 3-treated with zoledronic acid; and group 4-treated with zoledronic acid and LLLT. The zoledronic acid was administered at a dose of 0.035 mg/kg every 2 weeks for 8 weeks. Subsequently, bone defects of 2 mm were prepared in the tibias of all groups. The bone defects in groups 2 and 4 were irradiated with LLLT in the immediate post-operative period. After 14 and 28 days of application, the animals were submitted and euthanized for histomorphometric analysis. The results were submitted to statistical analysis (α = 5%), and the intragroup comparison was performed using the t test. On the other hand, for intergroup comparison, the ANOVA test was performed, and to the groups presenting statistically significant difference, the Student-Newman-Keuls test was used. In intergroup comparison, group 1 (mean ± SD= 45.2 ± 18.56%) showed a lower bone formation compared with groups 2 (64.13 ± 3.51%) (p = 0.358) and 4 (15.2 ± 78.22%) (p = 0.049), at the 14-day period. Group 3 (20.99 ± 7.42%) also presented a lower amount of neoformed bone tissue, with statistically significant difference when compared with groups 1 (p = 0.002), 2, and 4 (p ≤ 0,001). After 28 days, group 1 presented a lower amount of neoformed bone tissue compared with the other groups, with p = 0.020. Thus, it was concluded that LLLT associated with zoledronic acid is effective for stimulating bone formation in surgically created defects in rats, at the periods studied.


Assuntos
Terapia com Luz de Baixa Intensidade , Tíbia/efeitos dos fármacos , Tíbia/efeitos da radiação , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação , Ácido Zoledrônico/farmacologia , Animais , Feminino , Lasers Semicondutores , Osteogênese/efeitos dos fármacos , Osteogênese/efeitos da radiação , Osteotomia , Ratos Wistar , Tíbia/patologia
16.
Biomed Pharmacother ; 115: 108916, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054506

RESUMO

Lipopolysaccharide (LPS) can induce bone loss by stimulating osteoclast formation. Colony-stimulating factor 1 receptor (CSF 1R) inhibitors have great potential for the treatment of rheumatoid arthritis and tumor-related bone erosion. However, its role in LPS-induced bone loss is still not clarified. In this study, we observed the effects of CSF 1R inhibitor, PLX3397, on LPS-induced bone damage in an animal model. The models were established by LPS administration in male Sprague-Dawley rats. PLX3397 (30 mg/kg body weight) was given by oral gavage. MicroCT analysis, biomechanical properties, biomarker assay, histological examination, and mRNA expression of osteoclast differentiation-related genes (Traf6, Fra1, c-fos and NFATc1) were performed on the 8th week. LPS induced bone loss was shown as the decrease in bone volume fraction and trabecular number and increase in trabecular separation (p < 0.05). LPS exposure also markedly decreased the bone biomechanical properties. PLX3397 significantly abolished the LPS-induced bone microstructure damage (p < 0.05) and loss of biomechanical properties. PLX3397 also inhibited the increases of serum tartrate-resistant acid phosphatase 5b level enhanced by LPS (p < 0.05). PLX3397 attenuated the high expression of Traf6, Fra1, c-fos and NFATc1 stimulated by LPS. Our data demonstrated that PLX3397, a type of CSF 1R inhibitor, can suppress LPS-induced bone loss via the inhibition osteoclast formation.


Assuntos
Aminopiridinas/farmacologia , Reabsorção Óssea/prevenção & controle , Osteoclastos/efeitos dos fármacos , Osteoporose/prevenção & controle , Pirróis/farmacologia , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Animais , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/metabolismo , Osso Esponjoso/patologia , Modelos Animais de Doenças , Lipopolissacarídeos/farmacologia , Masculino , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteoporose/induzido quimicamente , Osteoporose/metabolismo , Osteoporose/patologia , Ratos Sprague-Dawley , Tíbia/efeitos dos fármacos , Tíbia/metabolismo , Tíbia/patologia
17.
Colloids Surf B Biointerfaces ; 181: 125-133, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128512

RESUMO

One of the events occurring when a biomaterial is implanted in an host is the protein deposition onto its surface, which might regulate cell responses. When a biomaterial displays a compromised biocompatibility, distinct complement pathways can be activated to produce a foreign body reaction. In this article, we have designed different types of biomaterial surfaces to study the inflammation process. Here, we used different concentrations of (3-glycidoxypropyl)-trimethoxysilane (GPTMS), an organically-modified alkoxysilane as a precursor for the synthesis of various types of sol-gel materials functionalizing coatings for titanium implants to regulate biological responses. Our results showed that greater GPTMS surface concentrations induced greater secretion of TNF-α and IL-10 on RAW 264.7 macrophages. When implanted into rabbit tibia, osseointegration decreased with higher GPTMS concentrations. Interestingly, higher deposition of complement-related proteins C-reactive protein (CRP) and ficolin-2 (FCN2), two main activators of distinct complement pathways, was observed. Taking all together, inflammatory potential increase seems to be GPTMS concentration-dependent. Our results show that a greater adsorption of complement proteins can condition macrophage polarization.


Assuntos
Materiais Biocompatíveis/farmacologia , Proteínas do Sistema Complemento/metabolismo , Macrófagos/efeitos dos fármacos , Silanos/farmacologia , Titânio/farmacologia , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Interleucina-10/biossíntese , Macrófagos/metabolismo , Camundongos , Tamanho da Partícula , Células RAW 264.7 , Coelhos , Silanos/síntese química , Silanos/química , Propriedades de Superfície , Tíbia/efeitos dos fármacos , Tíbia/metabolismo , Titânio/química , Fator de Necrose Tumoral alfa/biossíntese
18.
Acta Cir Bras ; 34(4): e201900408, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31066788

RESUMO

PURPOSE: To evaluate histologically and immunohistochemically the bone regeneration after application of simvastatin on tibial bone defects in rats. METHODS: Sixty Wistar albino rats were divided into 3 groups as control (6 mm tibial bone defect), defect + graft (allograft treatment), and defect + graft + simvastatin (10 mg/kg/day) for 28 days. RESULTS: Histopathological examination revealed inflammation in control group (defect group), congestion in blood vessels, and an increase in osteoclast cells. In defect + graft group, osteoclastic activity was observed and osteocyte cells were continued to develop. In defect + graft + simvastatin group, osteocytes and matrix formation were increased in the new bone trabeculae. Osteopontin and osteonectin expression were positive in the osteclast cells in the control group. Osteoblasts and some osteocytes showed a positive reaction of osteopontin and osteopontin. In defect + graft + simvastatin group, osteonectin and osteopontin expression were positive in osteoblast and osteocyte cells, and a positive expression in osteon formation was also seen in new bone trabeculae. CONCLUSION: The simvastatin application was thought to increase bone turnover by increasing the osteoinductive effect with graft and significantly affect the formation of new bone.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Sinvastatina/farmacologia , Tíbia/efeitos dos fármacos , Tíbia/cirurgia , Animais , Autoenxertos , Remodelação Óssea/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Osteoblastos , Osteoclastos , Ratos , Ratos Wistar , Tíbia/patologia
19.
Poult Sci ; 98(9): 3926-3936, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30938806

RESUMO

This study was conducted to determine the effects of residual superdoses of phytase on growth performance, tibia mineralization, and relative organ weight in ducks fed phosphorus-deficient diets. In Exp. 1, 4 kinds of commercial phytase were used to determine retention rate of phyatse with the phytase C being the highest via both high water-bath temperature (90%) and pelleting (50%), followed by phytase A, B, and D. In Exp. 2, a total of 560 male ducks were blocked based on body weight, and then allocated randomly to 7 treatments (5 replicates with 16 birds per replicate). Treatments included a maize-soybean meal-based diet with recommended calcium and 4.0 g non-phytate phosphorus (nPP)/kg starter diet or 3.8 g nPP/kg grower diet (positive control; PC), an nPP-deficient diet with 1.3 g nPP/kg starter diet or 1.1 g nPP/kg grower diet (negative control; NC), NC diets with increasing levels of residual phytase C (500, 1,000, 2,000, 3,000, and 4,000 units/kg feed) after pelleting. Birds fed NC diets had lower (P < 0.05) average daily gain (ADG) and average daily feed intake (ADFI) throughout the experiment compared with those fed PC diet. Supplementing NC diet with increasing residual superdoses of phytase improved (P < 0.05) ADG and ADFI quadratically in the entire experiment, while reduced feed-to-gain ratio (P < 0.05) quadratically during day 0 to 14. On day 14 and 35, birds fed NC diet had lower (P < 0.05) tibia length, weight, ash, calcium, phosphorus, and manganese contents than those fed PC diet. Increasing residual superdoses of phytase in NC diet increased (P < 0.05) tibia weight and ash, calcium, phosphorus contents quadratically on day 14 and 35. NC treatment increased (P < 0.05) the duodenum, jejunum, ileum, and cecum index compared with other treatments on day 14 and 35. Taken together, feeding increasing residual superdoses of phytase could counteract or exceed the negative effects of NC diet on growth performance, tibia mineralization, and relative organ weight in ducks.


Assuntos
6-Fitase/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Patos/fisiologia , Fósforo na Dieta/análise , Tíbia/efeitos dos fármacos , 6-Fitase/administração & dosagem , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Patos/crescimento & desenvolvimento , Masculino , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Tíbia/fisiologia
20.
Int J Biol Macromol ; 132: 811-821, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30946907

RESUMO

The present work describes in vitro and in vivo behaviors of thermosensitive composite hydrogels based on polymers/bioactive glass nanoparticles. Assays in SBF (simulated body fluid) solution showed that loss of hydrogel mass in vitro was decreased by 4.3% when bioactive glass nanoparticles (nBG) were incorporated, and confirmed the bioactivity of nBG containing hydrogels. In vitro assays demonstrated the cytocompatibility of the hydrogels with encapsulated rat bone marrow mesenchymal stem cells (BMSC). Crystal violet assays showed a 27% increase in cell viability when these cells were seeded in hydrogels containing nBG. In vivo biocompatibility was examined by injecting hydrogels into the dorsum of Swiss rats. The results indicated that the prepared hydrogels were nontoxic upon subcutaneous injection, and could be candidates for a safe in situ gel-forming system. Injection of the hydrogels into a rat tibial defect allowed preliminary evaluation of the hydrogels' regenerative potential. Micro Computed Tomography analysis suggested that more new tissue was formed in the defects treated with the hydrogels. Taken together, our data suggest that the developed injectable composite hydrogels possess properties which make them suitable candidates for use as temporary injectable matrices for bone regeneration.


Assuntos
Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Quitosana/química , Gelatina/química , Vidro/química , Hidrogéis/química , Nanocompostos/química , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Sobrevivência Celular/efeitos dos fármacos , Feminino , Injeções , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Ratos , Ratos Wistar , Tíbia/citologia , Tíbia/diagnóstico por imagem , Tíbia/efeitos dos fármacos , Tíbia/fisiologia , Engenharia Tecidual , Tecidos Suporte/química , Microtomografia por Raio-X
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