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1.
Int J Nanomedicine ; 15: 3605-3620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547017

RESUMO

Purpose: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field. Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections. Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head. Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/terapia , Glucocorticoides/efeitos adversos , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/citologia , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Hemólise/efeitos dos fármacos , Humanos , Indóis/química , Nanopartículas de Magnetita/toxicidade , Nanopartículas de Magnetita/ultraestrutura , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Polímeros/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Microtomografia por Raio-X , Proteína de Morte Celular Associada a bcl/metabolismo
2.
Georgian Med News ; (298): 21-27, 2020 Jan.
Artigo em Russo | MEDLINE | ID: mdl-32141842

RESUMO

Avascular necrosis of the femoral head is a multifactorial disease with progressive development of severe secondary coxarthrosis. There are two types of necroses - secondary and idiopathic. The pathogenesis of necrosis is associated with local blood circulation disorders, coagulopathies and violation of bone tissue regeneration. Usage of Steroids is one of the most often and important causes of non-traumatic osteonecrosis of the femoral head. Postulated pathogenetic mechanisms of steroid-induced osteonecrosis (ON) of the femoral head includes fat cell hypertrophy, fat emboli and intravascular coagulation. MRI stays the main diagnostic method for detection of osteonecrosis in the early stages. Preservation of the native hip is the goal of treatment in young and active patients. Early diagnosis and intervention prior to collapse of the femoral head is the key to a successful outcome of joint preserving procedures. There are no specific biomarkers for diagnostic of ON and NO "golden standard" for its treatment, and frequently a multidisciplinary approach becomes necessary. Joint replacement procedure remains as a main method of treatment after failure of joint preserving procedures and in cases of the late-stages of ON, involving collapse of the femoral head and degenerative changes of the acetabulum. More recent reports of hip replacement surgeries while osteonecrosis of the femoral head, have shown excellent results, but implant longevity and following revision surgeries, still remain an outstanding problem. In this article, there is described one of the latest clinical cases of the steroid induced avascular necroses of femoral head, which took place in our clinic. Positive clinical outcome, that means full physical and social rehabilitation of the patient, treated by total hip replacement confirms effectiveness of this method in treatment of above mentioned pathology.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Imagem por Ressonância Magnética , Esteroides/efeitos adversos , Artroplastia de Quadril , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/cirurgia , Humanos , Osteoartrite , Complicações Pós-Operatórias , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Esteroides/uso terapêutico
3.
Am J Phys Med Rehabil ; 99(4): e54-e55, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32195718

RESUMO

We outline a case in which osteonecrosis of the femoral head developed in temporal association with a single intra-articular injection of corticosteroid (triamcinolone acetonide) in a 72-yr-old woman, resulting in a total hip arthroplasty. We conclude that the risk of developing osteonecrosis after a single intra-articular injection of corticosteroid needs to be considered in the informed consent process.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/efeitos adversos , Injeções Intra-Articulares/efeitos adversos , Triancinolona Acetonida/efeitos adversos , Idoso , Artroplastia de Quadril , Feminino , Necrose da Cabeça do Fêmur/cirurgia , Glucocorticoides/administração & dosagem , Articulação do Quadril/cirurgia , Humanos , Triancinolona Acetonida/administração & dosagem
4.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502565

RESUMO

Bone marrow mesenchymal stem cells (BMSCs) play an important role in the process of bone repair. The present study investigated the effect of 5-azacytidine (AZA) and trichostatin A (TSA) on BMSC behaviors in vitro. The role of WNT family member 5A (WNT5A)/WNT family member 5A (WNT7A)/beta-catenin signaling was also investigated. BMSCs were isolated from a steroid-induced avascular necrosis of the femoral head (SANFH) rabbit model. The third-generation of BMSCs was used after identification. The results revealed obvious degeneration and necrosis in the SANFH rabbit model. AZA, TSA and TSA + AZA increased BMSC proliferation in a time-dependent fashion. AZA, TSA and TSA + AZA induced the cell cycle release from the G0/G1 phase and inhibited apoptosis in BMSCs. AZA, TSA and TSA + AZA treatment significantly decreased caspase-3 and caspase-9 activities. The treatment obviously increased the activity and relative mRNA expression of alkaline phosphatase. The treatment also significantly up-regulated the proteins associated with osteogenic differentiation, including osteocalcin and runt-related transcription factor 2 (RUNX2), and Wnt/beta-catenin signal transduction pathway-related proteins beta-catenin, WNT5A and WNT7A. The relative levels of Dickkopf-related protein 1 (an inhibitor of the canonical Wnt pathway) decreased remarkably. Notably, TSA + AZA treatment exhibited a stronger adjustment ability than either single treatment. Collectively, the present studies suggest that AZA, TSA and TSA + AZA promote cell proliferation and osteogenic differentiation in BMSCs, and these effects are potentially achieved via upregulation of WNT5A/WNT7A/b-catenin signaling.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Necrose da Cabeça do Fêmur/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Fosfatase Alcalina/genética , Animais , Azacitidina/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteonecrose/induzido quimicamente , Osteonecrose/patologia , Coelhos , Esteroides/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/genética
5.
Mol Med Rep ; 20(4): 3175-3181, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432121

RESUMO

At present, the molecular mechanism underlying the protective effect of Ginsenoside Rb1 remains unclear. The present study was designed to investigate whether Ginsenoside Rb1 weakened the steroid­induced avascular necrosis of the femoral head (SANFH) and to explore the possible mechanisms of the above effects. As a result, it was revealed that Ginsenoside Rb1 was protective against steroid­induced avascular necrosis and inhibited serum osteocalcin in a rat model of SANFH. Ginsenoside Rb1 reduced inflammation, oxidative stress and bone cell apoptosis in a rat model of SANFH. Furthermore, Ginsenoside Rb1 attenuated trabecula parameters, total cholesterol and low density lipoprotein/high density lipoprotein in SANFH rat. Additionally, Ginsenoside Rb1 significantly reversed alkaline phosphatase and osteocalcin activities, vascular endothelial growth factor (VEGF) receptor, VEGF, Runt related transcription factor 2 (Runx2) and bone morphogenetic protein (BMP)­2 protein expression in SANFH rat. Collectively, the present study demonstrated that Ginsenoside Rb1 attenuated SANFH through the VEGF/RUNX2/BMP­2 signaling pathway.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Necrose da Cabeça do Fêmur , Ginsenosídeos/farmacologia , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esteroides/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley
6.
J Orthop Surg Res ; 14(1): 226, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324193

RESUMO

BACKGROUND: Avascular necrosis of the femoral head (ANFH) is a severe complication after high-dose glucocorticoid (GC) administration. The pathogenesis of GC-induced ANFH remains unclear. Though the important role of endothelial progenitor cells (EPCs) in the progression of GC-induced ANFH has been noticed, the effects of GCs on EPCs and the underlying mechanism still need further study. METHODS: Circulating EPCs were obtained from the peripheral blood of ANFH patients and healthy controls by Ficoll-density gradient centrifugation. CD133+CD34+ cells with DiI-Ac-LDL uptake and FITC-UEA-1 binding were considered as EPCs. Number and functions of EPCs were analyzed by flow cytometry, chemotaxis assay, and tube formation assay. EPCs from healthy controls were also treated by different concentrations of methylprednisolone and prednisolone in vitro, and cell growth and angiogenic function were evaluated. Expression of CXCR7 and its downstream Akt/GSK-3ß/Fyn pathway were also analyzed by western blots after cells treated by methylprednisolone in vitro. RESULTS: The number and functions of EPCs in patients with GC-induced ANFH were significantly decreased. In vitro study showed for the first time that except extremely high concentrations, low to medium concentrations of GCs did not have significant effects on EPCs' growth. Methylprednisolone and prednisolone both inhibited angiogenesis of EPCs even at low concentrations. Mechanism studies found CXCR7 was downregulated in EPCs after methylprednisolone treatment in vitro. Expression and phosphorylation of Akt and GSK-3ß were also decreased with an upregulation of Fyn expression after steroid treatment. CONCLUSIONS: Our study showed that GC-induced ANFH patients have reduced the number and impaired functions of circulating EPCs. GCs did not show a significant effect on the growth of EPCs in vitro except extremely high concentrations of GCs. However, GCs significantly impaired EPC angiogenic function in vitro, even at low concentrations. Our study also suggested that downregulation of CXCR7 and its downstream Akt/GSK-3ß/Fyn pathway in EPCs might be a novel mechanism of how GCs suppress EPCs' angiogenesis.


Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Necrose da Cabeça do Fêmur/sangue , Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/efeitos adversos , Adulto , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Necrose da Cabeça do Fêmur/diagnóstico , Humanos , Masculino , Resultado do Tratamento , Adulto Jovem
7.
Orthop Surg ; 11(3): 481-486, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31243924

RESUMO

OBJECTIVE: The present study aimed to identify the relationship of α-2-macroglobulin and microvascular vessel pathology with steroid-induced femoral head necrosis in the Southeast Chinese population. METHODS: This study enrolled 40 patients diagnosed with steroid-induced necrosis of the femoral head. Patients had various stages of femoral head necrosis. The differential expression of serum proteins and mRNA from patients with steroid-induced necrosis of the femoral head (SINFH) and healthy volunteers was analyzed by western blot and quantitative polymerase chain reaction (QT-PCR). The pathological change in osteocyte necrosis was indicated by hematoxylin and eosin stain and immunohistochemistry. RESULTS: Hematoxylin and eosin stain showed histopathology changes in the necrotic area of patients with steroid-induced INFH: bone trabeculae were fewer and thinner, became broken, fragmented and structurally disordered; intraosseous adipose cells became enlarged; the arrangement of the osteoblasts became irregular; and vacant bone lacunae increased. QT-PCR showed significantly lower levels of α-2-macroglobulin in the serum of patients with SINFH than in controls (P < 0.05). Immunohistochemical staining and western blotting demonstrated that the expression of α-2-macroglobulin was significantly decreased in the necrotic area of SINFH patients (P < 0.05). CONCLUSION: The α-2-macroglobulin may be associated with the pathology of SINFH. The multiple pathological reactions occur in SINFH and α-2-macroglobulin may serve as a potential biomarker for the diagnosis of SINFH or a promising therapeutic target.


Assuntos
Corticosteroides/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Necrose da Cabeça do Fêmur/induzido quimicamente , Microvasos/patologia , alfa-Macroglobulinas/metabolismo , Adulto , Biomarcadores/sangue , Western Blotting , Estudos de Casos e Controles , China , Feminino , Necrose da Cabeça do Fêmur/sangue , Necrose da Cabeça do Fêmur/diagnóstico , Necrose da Cabeça do Fêmur/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
8.
J Orthop Res ; 37(11): 2348-2357, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31254413

RESUMO

Early diagnosis and prevention of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) continues to be a challenging problem for clinicians and researchers. However, the role of circulating biomarkers for GC-induced ONFH, which may reveal individual susceptibility and facilitate earlier diagnosis, remains to be determined. The aim of this study was to identify potential biomarkers that may predict early GC-induced ONFH. A total of 123 patients scheduled for initial systemic GC therapy were enrolled in this prospective nested case-control study. The serum concentrations of 13 potential biomarkers were measured in seven patients with GC-induced ONFH, diagnosed instantly after short-term use of GCs and in 20 controls who did not develop osteonecrosis despite similar GC therapy. Biomarkers were measured both before and after taking GCs to identify any differences in marker levels and the changes during GC therapy between two groups. Type I collagen cross-linked C-telopeptide (ß-CTX; p = 0.000) was significantly lower, high-density lipoprotein cholesterol (p = 0.092) and apolipoprotein (apo)-B/apo-A1 (p = 0.085) tended to be lower and higher, respectively, before GC treatment in osteonecrosis group. After GC therapy, ß-CTX (p = 0.014) was significantly lower and amino terminal telopeptide of procollagen type I (PINP; p = 0.068) tended to be lower in the osteonecrosis group. As secondary outcomes, we observed remarkable changes in nine potential biomarkers following short-term GC therapy in both groups. In conclusion, we found that ß-CTX, could potentially be used to predict GC-induced ONFH before GC therapy. Lower ß-CTX and PINP are promising biomarkers for the early diagnosis of GC-induced ONFH. These findings need to be confirmed in large-scale prospective studies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2348-2357, 2019.


Assuntos
Biomarcadores/sangue , Necrose da Cabeça do Fêmur/sangue , Glucocorticoides/efeitos adversos , Adolescente , Adulto , Estudos de Casos e Controles , Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/administração & dosagem , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
9.
Biomed Res Int ; 2019: 8298193, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192258

RESUMO

Background: Steroid-induced osteonecrosis of the femoral head is a relatively serious condition which seriously reduces patient quality of life. However, the pathogenesis of steroid-induced ONFH is still unclear. In recent years, more scholars have found that the pathogenesis of steroid-induced ONFH is related to susceptibility factors such as MMPs/TIMPs system. The main purpose of this study is to investigate the correlation between MMP2 and MMP10 gene polymorphisms and steroid-induced ONFH in Chinese Han population. Methods: Six SNPs in MMP2 and two SNPs in MMP10 were genotyped using Agena MassARRAY RS1000 system from 286 patients of steroid-induced ONFH and in 309 healthy controls. The association between MMP2 and MMP10 polymorphisms and steroid-induced ONFH risk were estimated by the Chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. The relative risk was estimated by odd ratios (ORs) and 95% confidence intervals (CIs). Result: We found that the minor TG allele of rs470154 in MMP10 was associated with an increased risk of steroid-induced ONFH (OR = 1.45, 95% CI, 1.03 - 2.05, p = 0.032). In the genetic model analysis, we found that rs2241146 in MMP2 gene and rs470154 in MMP10 gene showed a statistically significant association with increased risk of steroid-induced ONFH. The six SNPs (rs470154, rs243866, rs243864, rs865094, rs11646643, and rs2241146) showed a statistically significant association with different clinical phenotypes. Conclusion: Our results verify that genetic polymorphisms of MMP2 and MMP10 contribute to steroid-induced ONFH susceptibility in the population of Chinese Han population, and our study provides new insights into the role that MMP2 and MMP10 plays in the mechanism of ONFH.


Assuntos
Necrose da Cabeça do Fêmur , Predisposição Genética para Doença , Metaloproteinase 10 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Esteroides/efeitos adversos , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , China/etnologia , Feminino , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/etnologia , Necrose da Cabeça do Fêmur/genética , Humanos , Masculino , Pessoa de Meia-Idade , Esteroides/uso terapêutico
10.
Carbohydr Polym ; 214: 71-79, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30926009

RESUMO

In this study, one homogeneous polysaccharide (APP-AW), with an average molecular weight of 9550 Da, was purified from Agrimonia pilosa. Analysis by gas chromatography (GC), methylation, UV, Infrared spectra (IR), 1D and 2D nuclear magnetic resonance (NMR) spectroscopy indicated that APP-AW was a ß-(1 → 3)-d-glucan. The effect of APP-AW on dexamethasone (Dex)-induced apoptosis in osteoblasts was also examined. Pretreatment of APP-AW (100 µg/ml) significantly attenuated cell loss and apoptosis induced by Dex (1 µM) in osteoblasts as determined by MTT, Annexin V-FITC/ propidium iodide (PI) and Transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining assay. Collectively, the present study demonstrated that APP-AW might be an alternative therapeutics for the treatment of SANFH via reducing Dex­induced bone cellular apoptosis.


Assuntos
Agrimonia/química , Glucanos/farmacologia , Osteoblastos/efeitos dos fármacos , Componentes Aéreos da Planta/química , Animais , Apoptose/efeitos dos fármacos , Dexametasona , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/tratamento farmacológico , Glucanos/química , Glucanos/isolamento & purificação , Peso Molecular , Ratos
11.
Curr Med Sci ; 39(1): 75-80, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868494

RESUMO

Nowadays, the cumulative intake of glucocorticoids has become the most common pathogenic factor for non-traumatic osteonecrosis of the femoral head (ONFH). Apoptosis of osteoblasts is considered as the main reason of ONFH at the molecular level. Glycogen synthase kinase 3ß (GSK3ß) is an important regulator of cellular differentiation and apoptosis pathway, which can modulate the balance between osteoblasts and osteoclasts. Several studies have reported about its function in osteoporosis, but little is known about it in osteonecrosis. In our study, lipopolysaccharide and methylprednisolone were utilized to establish a rat ONFH model. The phosphorylation of GSK3ß Ser-9 was decreased in the model. Western blotting examination of ß-catenin, Bcl-2, Bax and caspase-3 revealed that the osteoblasts were apoptotic. In dexamethasone (Dex)-incubated primary osteoblasts, the expression profile of GSK3ß phosphorylation and apoptotic factors were consistent with those in the rat ONFH model. To further investigate the regulation of osteonecrosis caused by GSK3ß, the expression and function of GSK3ß were inhibited in Dex-incubated primary osteoblasts. The knockdown of GSK3ß by siRNA decreased the expression of Bax and cleaved caspase-3, but increased Bcl-2 and ß-catenin. On the other hand, selective inhibition of GSK3ß function by LiCl counteracted the activation of caspase-3 induced by Dex. Our work is the first study about the GSK3ß phosphorylation in ONFH, and provides evidence for further therapeutic methods.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Osteoartrite/induzido quimicamente , Osteoblastos/citologia , Serina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Dexametasona , Modelos Animais de Doenças , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/metabolismo , Técnicas de Silenciamento de Genes , Lipopolissacarídeos/efeitos adversos , Cloreto de Lítio/farmacologia , Metilprednisolona/efeitos adversos , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoblastos/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Regulação para Cima/efeitos dos fármacos
12.
Osteoporos Int ; 30(4): 871-877, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30852631

RESUMO

The purpose of this research was to examine if the IL1B gene polymorphism has impact on the risk of steroid-induced ONFH in Chinese population. We found that IL1B rs1143630 decreased the SANFH's risk and IL1B rs2853550 increased the risk of steroid-induced ONFH. So, we guess that IL1B gene influences the genetic susceptibility of steroid-induced ONFH. INTRODUCTION: Genetic polymorphisms in IL1B gene could be related in the pathogenesis of osteonecrosis. Discusses on the relationship between the IL1B gene and steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is still less in Chinese Han population. So, in this research, we want to examine whether the IL1B gene polymorphism has impact on the risk of steroid-induced ONFH in Chinese population. METHODS: A total of 286 steroid-induced ONFH patients and 441 controls were recruited, and seven SNPs (rs2853550, rs1143643, rs3136558, rs1143630, rs1143627, rs16944, and rs1143623) in IL1B gene were selected; unconditional logistic regression analysis was used to research the influence on the risk of steroid-induced ONFH. Functional annotations of IL1B variants were performed by RegulomeDB and HaploReg. RESULTS: rs1143630 (A>C) in the IL1B gene decreased the risk of steroid-induced ONFH in the allele model (OR = 0.69, 95%CI 0.51-0.93, p = 0.014). Further genetic model analyses found that IL1B rs2853550 AG genotype increased the risk of steroid-induced ONFH compared with the people who are carriers of the IL1B rs2853550 GG genotype (OR = 1.69, 95%CI 1.16-2.46, p = 0.012). In the dominant model, IL1B rs1143630 GG-GT genotype decreased the risk of steroid-induced ONFH (OR = 0.62, 95%CI 0.44-0.87, p = 0.0051). And further haplotype analysis was performed, while the result was not significant. Using RegulomeDB and HaploReg, rs2853550 is likely to affect TF binding, any motif and DNase peak. CONCLUSIONS: We guess that IL1B gene influences the genetic susceptibility of steroid-induced ONFH.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/genética , Glucocorticoides/efeitos adversos , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Necrose da Cabeça do Fêmur/epidemiologia , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
13.
BMC Musculoskelet Disord ; 20(1): 88, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30782153

RESUMO

BACKGROUND: The incidence of bilateral corticosteroid-induced osteonecrosis of the femoral head (ONFH) is high. Although the precise mechanism of corticosteroid-induced ONFH development is unclear, hepatic enzyme abnormalities such as low activity of hepatic cytochrome P450 3A could be one cause. Herein, we report the case of a patient who developed ONFH in the contralateral hip after the dose of corticosteroids for idiopathic thrombocytopenic purpura was increased. Liver biopsy was done to rule out autoimmune hepatitis. CASE PRESENTATION: A 32-year-old woman had been treated with continuous corticosteroids of up to 10 mg/day for Sjögren's syndrome for 25 years and corticosteroid-induced ONFH in the left side. At age 33, idiopathic thrombocytopenia developed, which was treated by increasing the corticosteroid dose (40 mg/day). Two months later, liver enzyme level began to increase slightly and continued to increase. A year after corticosteroid dose increase, contralateral ONFH developed, and a liver biopsy demonstrated nonalcoholic fatty liver disease (NAFLD). CONCLUSIONS: The current case indicates that corticosteroid dose increase is a potential risk factor for NAFLD and contralateral ONFH. Therefore, it would be useful and important for to screen and monitor patients with hepatic enzyme abnormality for ONFH occurrence.


Assuntos
Corticosteroides/efeitos adversos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/complicações , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/complicações , Adulto , Relação Dose-Resposta a Droga , Feminino , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Fatores de Risco
14.
BMJ Case Rep ; 12(2)2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30765453

RESUMO

Osteonecrosis, also known as avascular necrosis, is a condition that causes significant morbidity and loss of function. It is a common complication seen with supraphysiological steroid use. Early diagnosis is critical as it impacts prognosis. We report a 20-year-old man who developed bilateral osteonecrosis of the hip following 6 years of low-dose steroid replacement therapy for panhypopituitarism secondary to a transsphenoidal resection of a growth hormone-secreting pituitary macroadenoma. The patient presented with several weeks of right-sided hip pain and significant loss of function. X-ray and MRI showed bilateral osteonecrosis of the hips with the right side more severely affected than the left. He was initiated on analgesics and bisphosphonates and underwent right hip total arthroplasty followed 1 year later by left hip arthroplasty. Postsurgery, the patient is mobilising well and his pituitary hormones are well balanced. He continues on low-dose glucocorticoid replacement which will continue lifelong.


Assuntos
Necrose da Cabeça do Fêmur/terapia , Hipopituitarismo/tratamento farmacológico , Esteroides/efeitos adversos , Analgésicos/uso terapêutico , Artroplastia de Quadril/métodos , Difosfonatos/uso terapêutico , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Humanos , Hipopituitarismo/etiologia , Masculino , Neoplasias Hipofisárias/cirurgia , Resultado do Tratamento , Adulto Jovem
15.
J Orthop Surg Res ; 14(1): 11, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621711

RESUMO

OBJECTIVE: Psoralen is a natural plant toxin which has the function of protecting fungi, insects, and herbivores. In this study, we aim to investigate the effect and mechanism of psoralen on steroid-induced avascular necrosis of femoral head (SANFH). METHODS: Thirty rabbits were randomly divided into blank group (n = 10), model group (n = 10), and experimental group (n = 10). Rabbits in blank and model groups were treated with normal saline, and rabbits in experimental group were treated with psoralen. Total RNA of bone marrow was extracted by trizol, and the mRNA expression of PPARγ and osteocalcin were detected by q-PCR. Then, the mRNA expression of PPARγ and osteocalcin in the three groups were compared. Western blot was used to detect the PPARγ protein expression in the bone of rabbits. ELISA was used to measure the osteocalcin protein. RESULTS: The mRNA expression of PPARγ in model group significantly increased compared with blank group. The mRNA expression of osteocalcin in model group decreased compared with blank group. However, the mRNA and protein expressions of PPARγ in experimental group were significantly decreased compared with the model group. The protein expressions of osteocalcin increased compared with the model group. There was no significant difference of trabecular bone area (TBA) between experimental and blank groups (P > 0.05). TBA in model group was lower than the experimental group (P < 0.05). There was no significant difference of TBA between experimental and blank groups (P > 0.05). CONCLUSION: This research confirms that psoralen plays a positive role in the rehabilitation of SANFH.


Assuntos
Osso Esponjoso/metabolismo , Necrose da Cabeça do Fêmur/metabolismo , Ficusina/farmacologia , Osteocalcina/biossíntese , PPAR gama/biossíntese , Esteroides/toxicidade , Animais , Osso Esponjoso/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/tratamento farmacológico , Ficusina/uso terapêutico , Expressão Gênica , Osteocalcina/genética , PPAR gama/genética , Coelhos , Distribuição Aleatória
16.
Br J Radiol ; 92(1097): 20180822, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30676781

RESUMO

OBJECTIVE: Current therapies for multiple myeloma, which include corticosteroids, increase risk of avascular necrosis. The aim of this study was to assess incidental detection of femoral head avascular necrosis on routine whole body MRI including diffusion weighted MRI. METHODS: All whole body MRI studies, performed on patients with known multiple myeloma between 1 January 2010 to 1 May 2017 were assessed for features of avascular necrosis. RESULTS: 650 whole body MR scans were analysed. 15 patients (6.6%) had typical MR features of avascular necrosis: 2/15 (13.3%) had femoral head collapse, 4/15 (26.7%) had bilateral avascular necrosis and 9/15 (60%) were asymptomatic. CONCLUSION: This is the first report of avascular necrosis detected on routine whole body MRI in patients with multiple myeloma. Targeted review of femoral heads in multiple myeloma patients undergoing whole body MR is recommended, including in patients without symptoms. ADVANCES IN KNOWLEDGE: Whole body MR which includes diffusion-weighted MRI is extremely sensitive for evaluation of bone marrow. Although whole body MRI is primarily used for evaluation of multiple myeloma disease burden, it also presents an unique opportunity to evaluate the femoral heads for signs of avascular necrosis which can predate symptoms.


Assuntos
Imagem de Difusão por Ressonância Magnética , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Mieloma Múltiplo/diagnóstico por imagem , Imagem Corporal Total , Corticosteroides/efeitos adversos , Adulto , Idoso , Antineoplásicos/efeitos adversos , Diagnóstico Precoce , Feminino , Necrose da Cabeça do Fêmur/induzido quimicamente , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco
17.
J Arthroplasty ; 34(1): 163-168.e1, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30348552

RESUMO

BACKGROUND: Glucocorticoid usage, a leading cause of osteonecrosis of the femoral head (ONFH), and its prevalence was reported in 25%-50% of non-traumatic ONFH patients. Nevertheless, there have been no unified criteria to classify glucocorticoid-associated ONFH (GA-ONFH). In 2015, the Association Research Circulation Osseous addressed the issue of developing a classification scheme. METHODS: In June 2017, a task force was set up to conduct a Delphi survey concerning ONFH. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey consists of questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, the panel reached a consensus on the classification criteria. The response rates were 100% (Round 1), 96% (Round 2), and 100% (Round 3), respectively. RESULTS: The consensus on the classification criteria of GA-ONFH included the following: (1) patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period; (2) osteonecrosis should be diagnosed within 2 years after glucocorticoid usage, and (3) patients should not have other risk factor(s) besides glucocorticoids. CONCLUSION: Association Research Circulation Osseous established classification criteria to standardize clinical studies concerning GA-ONFH.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/classificação , Glucocorticoides/efeitos adversos , Comitês Consultivos , Consenso , Técnica Delfos , Necrose da Cabeça do Fêmur/etiologia , Humanos , Internacionalidade , Prednisolona/efeitos adversos , Fatores de Risco
18.
J Arthroplasty ; 34(1): 169-174.e1, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30348559

RESUMO

BACKGROUND: Although alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH) and its prevalence reportedly ranges from 20% to 45%, there are no unified classification criteria for this subpopulation. In 2015, Association Research Circulation Osseous decided to develop classification criteria for alcohol-associated ONFH. METHODS: In June of 2017, Association Research Circulation Osseous formed a task force to conduct a Delphi survey. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey included questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, consensus was reached on the classification criteria. The response rates for the 3 Delphi rounds were 100% (round 1), 96% (round 2), and 100% (round 3). RESULTS: The consensus on the classification criteria of alcohol-associated ONFH included the following: (1) patients should have a history of alcohol intake >400 mL/wk (320 g/wk, any type of alcoholic beverage) of pure ethanol for more than 6 months; (2) ONFH should be diagnosed within 1 year after alcohol intake of this dose; and (3) patients should not have other risk factor(s). CONCLUSION: ARCO-established classification criteria to standardize clinical studies concerning AA-ONFH.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Etanol/efeitos adversos , Necrose da Cabeça do Fêmur/classificação , Necrose da Cabeça do Fêmur/etiologia , Comitês Consultivos , Consenso , Técnica Delfos , Necrose da Cabeça do Fêmur/induzido quimicamente , Humanos , Internacionalidade , Fatores de Risco
19.
Drug Des Devel Ther ; 13: 45-55, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30587927

RESUMO

Background: Animal studies have demonstrated the therapeutic effect of mesenchymal stem cells (MSCs) on osteogenesis, but little is known about the functions of exosomes (Exos) released by bone MSCs (BMSCs). Here, we investigated the effect of BMSC Exos on steroid-induced femoral head necrosis (SFHN) and explored the vital genes involved in this process. Materials and methods: BMSCs were isolated from healthy and SFHN rats. BMSC Exos were isolated using the Exosome Precipitation Kit and characterized by transmission electron microscopy and Western blotting. SFHN BMSCs were incubated with Exos from healthy BMSCs. Osteogenic ability was assessed by oil red O staining and alizarine red staining. Differentially expressed genes (DEGs) induced by Exos were screened using the Osteogenesis RT2 Profiler PCR Array. The effect of upregulated Sox9 was examined using lentivirus-mediated siRNA. Results: The results revealed that BMSC Exos were 100-150 nm in size and expressed CD63. Moreover, BMSC Exo-treated SFHN cells exhibited suppressed adipogenesis compared to model cells. PCR array showed that eleven and nine genes were upregulated and downregulated, respectively, in the BMSC Exo-treated SFHN cells compared to the model group. Among the DEGs, osteogenesis-related genes, including Bmp2, Bmp6, Bmpr1b, Mmp9, and Sox9, may play important roles in SFHN. Furthermore, the DEGs were mainly involved in immune response, osteoblast differentiation, and in the transforming growth factor-ß/bone morphogenetic protein signaling pathway. The level of the SOX9 protein was upregulated by Exos, and Sox9 silencing significantly decreased the osteogenic effect of BMSC Exos. Conclusion: Our data suggest that Exos derived from BMSCs mainly affect SFHN osteogenesis, and this finding can be further investigated to develop a novel therapeutic agent for SFHN.


Assuntos
Dexametasona/toxicidade , Exossomos/metabolismo , Necrose da Cabeça do Fêmur/terapia , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Animais , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 6/genética , Proteína Morfogenética Óssea 6/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Células Cultivadas , Exossomos/ultraestrutura , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/fisiopatologia , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/ultraestrutura , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Transdução de Sinais
20.
Biochem Biophys Res Commun ; 509(1): 255-261, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30579595

RESUMO

PURPOSE: large doses of glucocorticoids (GCs) are the most common cause of glucocorticoid-induced osteonecrosis of femoral head (GIONFH). Although awareness of GIONFH among patients with GCs history has increased over recent years, several studies indicate that its mechanism remains unclear. METHODS: To evaluate the function of circUSP45 in GIONFH, femoral heads in GIONFH patients or femoral heads in fracture patients were collected. In vitro, RT-PCR, FISH, RNA pull down and Western blotting assay were used to evaluate the function of circUSP45. In addition, we also verified the effects of circUSP45 on osteogenesis using alizarin red staining. In vivo, we used HE staining and microCT analysis to evaluate the bone mass. Moreover, the mechanism of circUSP45 regulating osteogenesis through the miR-127-5p/PTEN/AKT pathway was also investigated. RESULTS: The results showed that expression of circUSP45 increased in GIONFH patients. The overexpression of circUSP45 decreases osteogenic gene expression and inhibits the proliferation of BMSCs. Furthermore, circUSP45 was located mainly in the cytoplasm and directly interacted with miR-127-5p. MiR-127-5p acts with its targets PTEN to regulate the osteogenesis. MicroCT and HE staining verify the function of circUSP45 in GIONFH rat model. CONCLUSION: CircUSP45 decreases osteogenesis in bone GIONFH by sponging miR-127-5p through PTEN/AKT signal pathway.


Assuntos
Necrose da Cabeça do Fêmur/genética , MicroRNAs/genética , Osteogênese , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA/genética , Animais , Células Cultivadas , Feminino , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/patologia , Regulação da Expressão Gênica , Glucocorticoides , Humanos , RNA Circular , Ratos Sprague-Dawley , Transdução de Sinais
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