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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.
J Sports Sci Med ; 18(4): 596-603, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31827343

RESUMO

This study aimed to investigate the expression of PGC-1α/FNDC5/irisin induced by attenuation of high-fat diet (HFD)-induced bone accrual and determine whether swimming exercise could improve attenuating bone accrual through this mechanism. Eight-week-old Sprague-Dawley rats were divided into two groups for the first 8 weeks: CD, control diet (n = 10); and HFD, high-fat diet (n = 20). HFD-fed rats were again divided into two groups for further 8 weeks treatment: HFD (n = 10) and HFD with swimming exercise (HEx, n = 10). During this time, the CD group continuously fed the normal diet. Throughout the 16 weeks study period, the rats were weighed once every week. Samples were collected for analysis after last 8 weeks of treatment in the 16 weeks. Morphological and structural changes of the femur and tibial bone were observed using micro-CT, and Osteocalcin, CTX-1 and irisin levels in the blood were measured by enzyme-linked immunosorbent assay. The expression of IL-1, ß-catenin, FNDC5 and PGC-1α, in the femur were evaluated by immunohistochemistry. Eight weeks of HFD increased body weight and epididymal fat mass and decreased bone mineral density (BMD). Subsequent 8 weeks of swimming exercise improved obesity, BMD, bone microstructure, and bone metabolic factors in the HEx group. The irisin levels in the blood and the expressions of FNDC5 and PGC-1α in the bone were significantly lower in the HFD group than in the CD group, but elevated in the HEx group than in the HFD group. Swimming exercise is effective in improving obesity-worsened bone health and increases blood irisin and bone PGC-1α and FNDC5 levels.


Assuntos
Osso e Ossos/metabolismo , Dieta Hiperlipídica , Fibronectinas/metabolismo , Osteoporose/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Natação/fisiologia , Animais , Distribuição da Gordura Corporal , Osso e Ossos/anatomia & histologia , Osso e Ossos/diagnóstico por imagem , Ciguatoxinas/sangue , Modelos Animais de Doenças , Fêmur/anatomia & histologia , Fêmur/metabolismo , Fibronectinas/sangue , Humanos , Interleucina-1/metabolismo , Masculino , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/etiologia , Distribuição Aleatória , Ratos Sprague-Dawley , Tíbia/anatomia & histologia , Tíbia/metabolismo , Microtomografia por Raio-X , beta Catenina/metabolismo
4.
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
5.
Bone Joint J ; 101-B(8): 915-921, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31362550

RESUMO

AIMS: Altered alignment and biomechanics are thought to contribute to the progression of osteoarthritis (OA) in the native compartments after medial unicompartmental knee arthroplasty (UKA). The aim of this study was to evaluate the bone activity and remodelling in the lateral tibiofemoral and patellofemoral compartment after medial mobile-bearing UKA. PATIENTS AND METHODS: In total, 24 patients (nine female, 15 male) with 25 medial Oxford UKAs (13 left, 12 right) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively and at one and two years postoperatively, along with standard radiographs and clinical outcome scores. The mean patient age was 62 years (40 to 78) and the mean body mass index (BMI) was 29.7 kg/m2 (23.6 to 42.2). Mean osteoblastic activity was evaluated using a tracer localization scheme with volumes of interest (VOIs). Normalized mean tracer values were calculated as the ratio between the mean tracer activity in a VOI and background activity in the femoral diaphysis. RESULTS: Significant reduction of normalized tracer activity was observed one year postoperatively in tibial and femoral VOIs adjacent to the joint line in the lateral compartment. Patellar VOIs and remaining femoral VOIs demonstrated a significant, diminished normalized tracer activity at final follow-up. CONCLUSION: The osteoblastic bone activity in the native compartments decreased significantly after treatment of medial end-stage OA with a UKA, implying reduced stress to the subchondral bone in the retained compartments after a UKA. Cite this article: Bone Joint J 2019;101-B:915-921.


Assuntos
Artroplastia do Joelho/efeitos adversos , Fêmur/metabolismo , Hemiartroplastia/efeitos adversos , Articulação do Joelho/metabolismo , Osteoartrite do Joelho/cirurgia , Osteoblastos/metabolismo , Tíbia/metabolismo , Adulto , Idoso , Artroplastia do Joelho/instrumentação , Artroplastia do Joelho/métodos , Biomarcadores/metabolismo , Remodelação Óssea , Feminino , Fêmur/diagnóstico por imagem , Seguimentos , Hemiartroplastia/instrumentação , Hemiartroplastia/métodos , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Estudos Prospectivos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tíbia/diagnóstico por imagem , Resultado do Tratamento
6.
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
7.
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
8.
Curr Med Sci ; 39(4): 604-608, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346997

RESUMO

Children presenting with partial physeal arrest and significant remaining growth may benefit from physeal bar resection, although the operation is a technique demanding procedure. This study evaluates the treatment of post-traumatic pediatric ankle varus deformity using physeal bar resection and hemi-epiphysiodesis with the assistance of two operative methods. Forty-five patients presenting with a distal tibial medial physeal bridge as well as ankle varus deformity following traumatic ankle physeal injury between 2009 and 2017 were followed. These patients were treated with physeal bar resection and hemi-epiphysiodesis, with the assistance of either fluoroscopy (10 cases) or intraoperative three-dimensional navigation (35 cases). Of the 45 cases, the median age was 9.0 years (range: 3-14 years) with 28 male and 17 female patients. The median of pre-operation ankle varus angle was 20 degrees (IQR 15-25) and 5 degrees (IQR 0-20) at the time of final follow up, representing a statistically significant difference (P<0.05). No differences were observed with regards to age, gender, and surgical history between effective group and ineffective group (P>0.05). The median of pre-operative ankle varus angles of the navigation and fluoroscopy groups were both 20 degrees (P>0.05). The median correction angle of the navigation and fluoroscopy groups was 10 and 15 degrees, respectively (P>0.05). Our results indicate that physeal bar resection and hemiepiphysiodesis are effective treatments for correcting ankle varus deformity due to traumatic medial physeal arrest of the distal tibia. We observe no difference in outcome between fluoroscopy group and three-dimensional navigation group during the procedures.


Assuntos
Tornozelo/patologia , Lâmina de Crescimento/metabolismo , Metatarso Varo/terapia , Tíbia/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Lâmina de Crescimento/patologia , Humanos , Masculino , Metatarso Varo/genética , Metatarso Varo/patologia , Período Pré-Operatório , Tíbia/patologia , Resultado do Tratamento
9.
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
10.
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
11.
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
12.
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
13.
PLoS One ; 14(5): e0217509, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31136626

RESUMO

The effect of hempseed in the diet of laying hens was evaluated at 0, 30, 60 and 90 g/kg concentrations. The aim of the study was to determine the effect of dietary treatment on the performance of hens, the physical characteristics of egg quality, the concentrations of α- and γ-tocopherol and the carotenoid and cholesterol contents of egg yolks, together with the breaking strength of tibial measurements. In light of the obtained results, our study aimed to address the optimal dietary level of hempseed in laying hen diets. Lohmann Brown hens (n = 240) were divided into 4 dietary treatment groups (6 cages per treatment) with 10 hens per cage. The experiment lasted for 12 weeks. The level of nutrients in all diets (wheat-corn) was well balanced. The dietary metabolisable energy was adjusted using rapeseed oil. The addition of 30 g/kg of hempseed to the diet significantly increased (P˂0.001) egg production and egg mass. Alpha-tocopherol increased significantly (P = 0.002) only in the case of the 60 g/kg hempseed level (101 mg/kg dry matter (DM) versus 83 mg/ kg DM in the control group). In contrast, the level of γ-tocopherol increased gradually from 11 mg/kg DM in the control to 29, 39 and 43 mg/kg DM at the 30, 60 and 90 g/kg levels of dietary hempseed, respectively. The concentrations of beta carotene, zeaxanthin and lutein in egg yolks were not influenced by the dietary treatment. Hempseed at 90 g/kg (P = 0.036) decreased egg shell thickness without affecting its strength. The addition of hempseed decreased (P˂0.001) the cholesterol concentration in the egg yolks in all experimental groups. The addition of 30, 60 and 90 g hempseed increased (P˂0.001) the breaking strength of the tibia to 354, 352 and 350 N, respectively, compared to 297 N in the control group. The highest level of hempseed in the diet positively influenced the Ca concentration in the tibia (P = 0.021). The concentration of P in the tibia was negatively affected in the 60 to 90 g/kg hempseed treatments (P˂0.001). Eggs are a significant source of α-tocopherol. Based on our results, there is a possibility for enrichment of egg yolks with γ-tocopherol, with all of its associated health benefits, by the addition of hempseed to the diet of laying hens. Another significant benefit of hempseed is its effect on the breaking strength of the tibia, which can help with crucial problems in the commercial breeding of laying hens.


Assuntos
Ração Animal , Cannabis , Galinhas/crescimento & desenvolvimento , Gema de Ovo/metabolismo , Sementes , Tíbia/metabolismo , gama-Tocoferol/metabolismo , Animais , Feminino
14.
PLoS One ; 14(4): e0215405, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30995279

RESUMO

Alterations of structure and density of cortical bone are associated with fragility fractures and can be assessed in vivo in humans at the tibia. Bone remodeling deficits in aging women have been recently linked to an increase in size of cortical pores. In this ex vivo study, we characterized the cortical microarchitecture of 19 tibiae from human donors (aged 69 to 94 years) to address, whether this can reflect impairments of the mechanical competence of the proximal femur, i.e., a major fracture site in osteoporosis. Scanning acoustic microscopy (12 µm pixel size) provided reference microstructural measurements at the left tibia, while the bone vBMD at this site was obtained using microcomputed tomography (microCT). The areal bone mineral density of both left and right femoral necks (aBMDneck) was measured by dual-energy X-ray absorptiometry (DXA), while homogenized nonlinear finite element models based on high-resolution peripheral quantitative computed tomography provided hip stiffness and strength for one-legged standing and sideways falling loads. Hip strength was associated with aBMDneck (r = 0.74 to 0.78), with tibial cortical thickness (r = 0.81) and with measurements of the tibial cross-sectional geometry (r = 0.48 to 0.73) of the same leg. Tibial vBMD was associated with hip strength only for standing loads (r = 0.59 to 0.65). Cortical porosity (Ct.Po) of the tibia was not associated with any of the femoral parameters. However, the proportion of Ct.Po attributable to large pores (diameter > 100 µm) was associated with hip strength in both standing (r = -0.61) and falling (r = 0.48) conditions. When added to aBMDneck, the prevalence of large pores could explain up to 17% of the femur ultimate force. In conclusion, microstructural characteristics of the tibia reflect hip strength as well as femoral DXA, but it remains to be tested whether such properties can be measured in vivo.


Assuntos
Absorciometria de Fóton , Densidade Óssea , Osso Cortical , Colo do Fêmur , Tíbia , Microtomografia por Raio-X , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso Cortical/diagnóstico por imagem , Osso Cortical/metabolismo , Feminino , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Porosidade , Tíbia/diagnóstico por imagem , Tíbia/metabolismo
15.
Ecotoxicol Environ Saf ; 175: 83-89, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30889403

RESUMO

Tetramethyl thiuram disulfide (thiram) is a dithiocarbamate, which is widely used on seeds and storing food grains. The incorporation of thiram into the food chain could be a risk for both human beings and animals. Thiram-contaminated feed has been considered a common cause of tibial dyschondrolplasia (TD) in many avian species. The molecular mechanism of action of thiram on TD involving microRNA (miRNA) is not fully understood. For this purpose, the morbidity and pathologic changes were evaluated to understand the TD, and high-throughput RNA sequencing (RNA-Seq) was performed to explore the differentially expressed miRNAs (DEGs). RT-qPCR was used to confirm the validity as compared with sequencing data. The results showed that the marked alterations in the growth plate of the TD chickens were noticeable, with shrinking cells and irregular chondrocyte columns as compared with control group. In this study, we identified total 375 (p < 0.1), 340 (p < 0.05) and 266 (p < 0.01) significant DEGs between the TD and control groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs showed that the target miRNAs were significantly enriched in different treatment groups, such as apoptosis, mRNA surveillance pathway, mitophagy-animal, etc. This study provides theoretical basis for in-depth understanding the pathogenesis of thiram-induced TD and explore the new insights towards the proposed molecular mechanism of specific miRNA as biomarkers for effective gene diagnosis and treatment of TD in broilers.


Assuntos
Galinhas , Poluentes Ambientais/toxicidade , MicroRNAs/genética , Osteocondrodisplasias/induzido quimicamente , Doenças das Aves Domésticas/induzido quimicamente , Tiram/toxicidade , Tíbia/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Galinhas/genética , Lâmina de Crescimento/efeitos dos fármacos , Lâmina de Crescimento/metabolismo , Lâmina de Crescimento/patologia , MicroRNAs/metabolismo , Osteocondrodisplasias/veterinária , Doenças das Aves Domésticas/metabolismo , Tíbia/metabolismo , Tíbia/patologia , Transcriptoma/efeitos dos fármacos
16.
J Mol Histol ; 50(3): 229-237, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30927131

RESUMO

At present, a few studies have been done on the changes in the distribution, morphology and quantity of mechanoreceptors in anterior cruciate ligament (ACL) with age. In this study, we observed the changes in mechanoreceptors of healthy rabbits' ACL with age. We found that rabbits' ACLs contained 5 kinds of mechanoreceptors including Ruffini corpuscles, Pacinian corpuscles, Golgitendon bodies, free nerve endings and atypical mechanoreceptors. In each ACL, free nerve endings were the most followed by Ruffini corpuscles, Pacinian corpuscles, Golgitendon bodies and atypical mechanoreceptors in the younger than one-old rabbits. Most of the mechanoreceptors were distributed in the synovium near the attachment points of ACL with the femur and tibia. The total quantity of mechanoreceptors were the most in the 3- and 6-month groups, but did not show a significant difference between the two group (P > 0.05). However, there were significant differences in the total quantity of mechanoreceptors between other groups (all P < 0.05). RT-PCR indicated that NEFM and S100B levels increased with age, and reached a peak in the 1-year group with significant differences as compared to other groups. NEFM and S100B levels were the second in 6-month and 2-year groups and the lowest in the 1-week group. We can conclude that in rabbits' ACLs, free nerve endings are the most common, followed by Ruffini corpuscles, Pacinian corpuscles and Golgitendon bodies. The total quantity of mechanoreceptors reaches a peak in 3 months, while NEFM and S100B reach a peak in 1 year.


Assuntos
Envelhecimento/genética , Proteínas de Neurofilamentos/genética , Subunidade beta da Proteína Ligante de Cálcio S100/genética , Tíbia/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Ligamento Cruzado Anterior/metabolismo , Ligamento Cruzado Anterior/patologia , Modelos Animais de Doenças , Humanos , Mecanorreceptores/metabolismo , Coelhos , Tíbia/patologia
17.
J Ethnopharmacol ; 236: 108-113, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30849503

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional Korean medicine theory in which children's growth retardation is attributed to blood deficiency, Siwu decoction (SWD), a representative treatment for blood deficiency, was chosen as a sample. AIM OF THE STUDY: To evaluate the effects of SWD on chondrocyte proliferation of growth plate in adolescent female rats. MATERIALS AND METHODS: Female adolescent rats were allocated to one of the following four groups; SWD 100 and 300 mg/kg, recombinant human growth hormone, and vehicle for 4 days. Tetracycline was intraperitoneally injected at 48 h before sacrifice to obtain a band exhibiting fluorescence by binding newly formed bone. Bromodeoxyuridine was injected at day 2-4 to mark proliferating chondrocytes. To evaluate possible mechanisms of SWD, expressions of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in the growth plate were examined by immunohistochemistry. RESULTS: Treatment with SWD significantly increased the number of BrdU-positive chondrocytes and the new bone formation in the proximal growth plate of tibia compared to the vehicle treated control group. SWD also increased the expression of IGF-1 and BMP-2 in the proliferative and hypertrophic zones of the growth plate. CONCLUSIONS: SWD 300 mg/kg stimulates chondrocyte proliferation and new bone formation in the growth plate. Immunohistochemical studies indicate that the effects of SWD may be due to upregulation of local IGF-1 and BMP-2 expression in the growth plate, which may be considered as a GH-dependent paracrine-autocrine pathway.


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Lâmina de Crescimento/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Proteína Morfogenética Óssea 2/biossíntese , Condrócitos/metabolismo , Relação Dose-Resposta a Droga , Feminino , Lâmina de Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/biossíntese , Medicina Tradicional Coreana , Ratos , Ratos Sprague-Dawley , Tíbia/efeitos dos fármacos , Tíbia/metabolismo
18.
Int J Mol Sci ; 20(5)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871109

RESUMO

Eleutherococcus extract mixture (EEM) is an herbal mixture of dried stem of Eleutherococcus sessiliflorus and germinated barley, which has been highly effective, in previous screening and among the traditional medicines to tonify innate qi and acquired qi, respectively. In this study, we investigate the effects of EEM on endochondral bone formation. Female adolescent rats were given EEM, growth hormone or vehicle for 10 days. Tetracycline was intraperitoneally injected to light the fluorescent band 72 h before sacrifice to determine endochondral bone formation. In order to evaluate endocrine or paracrine/autocrine mechanisms, expressions of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), or bone morphogenetic protein 2 (BMP2) were evaluated after EEM administration in liver or growth plate (GP). EEM oral administration significantly increased endochondral bone formation and proliferative and hypertrophic zonal heights of tibial GP. EEM also upregulated hepatic IGF1 and IGFBP3 mRNA expressions, and IGF1 and BMP2 expressions in GP. Taken together, EEM increases endochondral bone formation through stimulating proliferation and hypertrophy with upregulation of hepatic IGF1 and IGFBP3 expressions. Considering immunohistochemical studies, the effect of EEM may be due to increased local IGF1 and BMP2 expression in GP, which may be considered growth hormone (GH)-dependent endocrine and autocrine/paracrine pathways.


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Eleutherococcus/química , Osteogênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tíbia/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/metabolismo , Proliferação de Células/efeitos dos fármacos , Condrócitos/metabolismo , Feminino , Hormônio do Crescimento/metabolismo , Lâmina de Crescimento/efeitos dos fármacos , Lâmina de Crescimento/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Tíbia/metabolismo
19.
PLoS One ; 14(2): e0210402, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30707699

RESUMO

Orthopedic device-related infection (ODRI) is a potentially devastating complication arising from the colonization of the device with bacteria, such as Staphylococcus aureus. The aim of this study was to determine if intraoperative loading of a clinically approved calcium phosphate (CaP) coating with gentamicin can protect from ODRI in vivo. First, CaP-coated titanium aluminium niobium (TAN) discs were used to investigate the adsorption and release kinetics of gentamicin in vitro. Gentamicin loading and subsequent release from the coating were both rapid, with maximum loading occurring following one second of immersion, and >95% gentamicin released within 15 min in aqueous solution, respectively. Second, efficacy of the gentamicin-loaded CaP coating for preventing ODRI in vivo was investigated using a CaP-coated unicortical TAN screw implanted into the proximal tibia of skeletally mature female Wistar rats, following inoculation of the implant site with S. aureus. Gentamicin-loading prevented ODRI in 7/8 animals, whereas 9/9 of the non-gentamicin treated animals were infected after 7 days. In conclusion, gentamicin can be rapidly and simply loaded onto, and released from, CaP-based implant coatings, and this is an effective strategy for preventing peri-operative S. aureus-induced ODRI in vivo.


Assuntos
Fosfatos de Cálcio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Gentamicinas/farmacologia , Cuidados Intraoperatórios , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/crescimento & desenvolvimento , Ligas/farmacologia , Animais , Parafusos Ósseos , Feminino , Nióbio/farmacologia , Ratos , Ratos Wistar , Tíbia/metabolismo , Tíbia/microbiologia , Tíbia/patologia
20.
Arch Oral Biol ; 99: 73-81, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30640030

RESUMO

OBJECTIVE: To evaluate the effect of sympathetic nervous system hyperactivity on craniofacial skeletal growth in growing spontaneously hypertensive rats (SHRs). DESIGN: Craniofacial skeletal growth was compared between male SHR and Wistar-Kyoto rats (WKR) using linear measurements on lateral and transverse cephalometric radiographs at the age of 12 weeks. Tibia length was measured as an index of whole body growth. Body weight and blood pressure were measured from 3 to 12 weeks of age. Bone microstructure in the mandibular condyle and tibia between the two groups was compared at the age of 12 weeks using microcomputed tomography. RESULTS: The SHRs had a significantly lower body weight than WKRs from 7 weeks of age, and tibial length was significantly smaller in the SHRs than in the WKR at 12 weeks of age. In all SHRs, blood pressure was significantly higher than in WKRs from 3 to 12 weeks of age. Cephalometric analyses revealed decreased measurements of the neurocranium, viscerocranium, and mandible in SHRs, and mandibular growth was most negatively affected in this group. Lastly, in SHRs, microcomputed tomography analyses revealed decreased bone mineral density and bone volume/tissue volume in the mandibular condyle but not in the tibia. CONCLUSION: In growing SHRs, hypertension related to the hyperactivity of the sympathetic nervous system reduced craniofacial skeletal growth more than the growth of the tibia.


Assuntos
Ossos Faciais/crescimento & desenvolvimento , Hipertensão/complicações , Sistema Nervoso Simpático/metabolismo , Tíbia/crescimento & desenvolvimento , Animais , Pressão Sanguínea , Peso Corporal , Densidade Óssea , Ossos Faciais/diagnóstico por imagem , Ossos Faciais/metabolismo , Masculino , Côndilo Mandibular/crescimento & desenvolvimento , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Tíbia/diagnóstico por imagem , Tíbia/metabolismo , Microtomografia por Raio-X
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