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1.
Medicine (Baltimore) ; 99(13): e19368, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221063

RESUMO

BACKGROUNDS: Femoral head necrosis is one of the most common orthopedic diseases which can be diagnosed in all ages with different reasons. Taohong Siwu decoction (TSD) has been widely used in the treatment of femoral head necrosis. However, as far as we know, there is still a lack of supporting evidence regarding the efficacy of TSD for femoral head necrosis. Therefore, this protocol aims to evaluate the effectiveness and safety of TSD for femoral head necrosis. METHODS: Eight electronic databases, including PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Technology Periodical database, (Chinese Scientific Journal Database) and Wanfang Database will be searched from the time when the respective databases were established to January 2020. Randomized controlled trials of TSD in the treatment of femoral head necrosis will be collected. After evaluating the quality of methodology and extracting valid data, the final meta-analysis will be carried out with software Revman 5.3. ETHICS AND DISSEMINATION: The results of this systematic review will offer implications of the use of TSD treatment for Femoral Head Necrosis. It uses aggregated published data instead of individual patient data and does not require an ethical board review and approval. The findings will be published in a peer-reviewed journal and disseminated in conference presentations. RESULTS: The results of this study will offer implications of the use of TSD treatment for FHN with this meta-analysis. CONCLUSION: The conclusion of this study will provide recent evidence to assess whether TSD is effective and safe in the treatment of FHN.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Necrose da Cabeça do Fêmur/tratamento farmacológico , China , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
2.
Zhongguo Gu Shang ; 32(11): 1003-1007, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31870047

RESUMO

OBJECTIVE: To observe clinical efficacy of Yishen Huoxue decoction(YSHXD) for the treatment of non-traumatic osteonecrosis of femoral head at early and middle stage. METHODS: From January to June 2016, 69 patients (72 hips) with non-traumatic osteonecrosis of femoral head at early and middle stage were divided into treatment group and control group according to therapeutic methods. In treatment group, there were 35 patients 43 hips, including 15 males and 20 females, aged from 28 to 62 years old with an average of(41.80±11.03) years old, 6 hips were at the stage I, 27 hips were at the stageII, 10 hips were at the stage IIIa according to ARCO classification; and treated by using YSHXD, one dose a day for 12 months. In control group, there were 34 patients 39 hips, including 16 males and 18 females, aged from 31 to 61 years old with an average of (43.35±13.52) years old, 5 hips were at the stage I, 26 hips were at the stageII, 8 hips were at the stage IIIa according to ARCO classification; and treated by using alendronate sodium tablets 70 mg every week for 12 months. Preoperative and postoperative HSS score at 2 weeks were observed and compared, EQ-5D index was used to compare clinical effects. ARCO classification was applied to imaging evaluation, the stage of ARCO over IIIa was considered as end point of observation. The final following-up time and ARCO classification were recorded and performed Kaplan-Meier survival analysis. RESULTS: All patients were followed-up from 26 to 76 months with an average of(43.50±13.26) months. Postoperative Harris score at 2 years in treatment group (84.92±7.56) was higher than that of before treatment (73.58±10.02) (P<0.05), and higher than that of control group(79.61±10.92)(P<0.05), especially the scores of joint function and activity were higher than those of control group(P<0.05). EQ-5D index in treatment group 0.66±0.12 was higher than that of control group 0.59±0.12(P<0.05). Nine hips were collapsed in treatment group at final follow-up, and 10 hips were collapsed in control group, and had no statistical difference between two groups (P>0.05). There was no statistical difference in kaplan-meier survival analysis curves between two groups (P>0.05). There were statistical difference in survival rate between the early, middle ARCO stage and different Harris evaluation. CONCLUSIONS: YSHXD for the treatment of non-traumatic osteonecrosis of femoral head at early and middle stage has obviously clinical effects, could improve hip joint function, and quality of life, and delay the process of femoral head necrosis collapse.


Assuntos
Medicamentos de Ervas Chinesas , Necrose da Cabeça do Fêmur , Adulto , Transplante Ósseo , Feminino , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/tratamento farmacológico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
3.
Orthop Surg ; 11(6): 1209-1219, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31692295

RESUMO

OBJECTIVE: To use Gene Expression Omnibus (GEO) database coupled with Connectivity Map (CMap) databases to screen potential therapeutic drugs for osteonecrosis of femoral head (ONFH) rapidly. METHODS: Raw genetic data with accession number GSE74089 that contained eight hip articular cartilage specimens from four ONFH patients and four healthy controls were obtained from the Gene Expression Omnibus (GEO) database and were then integrated using R to identify differentially expressed genes (DEGs). Subsequently, to identify several potential small molecular compounds that were most strongly negatively correlated with ONFH, a search query of DEGs was explored by using CMap. RESULTS: Filtering revealed 1937 DEGs with log (fold-change) ≥1 and adjust P value < 0.001. Finally, a network of candidate targets for ONFH with 135 nodes and 660 edges was constructed through network topology analysis, including 96 up-regulated genes and 39 down-regulated genes. Several significant gene functions and signaling pathways associated with pathological processes of ONFH were identified via gene enrichment analysis. Based on the CMap database, some potential small molecular components that may be possible to counteract the effects of molecular signal imbalance for ONFH were identified. Neostigmine bromide with low CMap score and P value and specificity score was predicted to be the most candidate compound, involved in the "positive regulation of stem cell proliferation," "regulation of protein autophosphorylation," "VEGF signaling pathway," and "ECM-receptor interaction." CONCLUSIONS: The GEO and CMap databases can be effectively used in understanding the molecular changes in ONFH and provide a systematic manner to identify potential drugs for ONFH prevention and treatment. However, additional clinical and experimental research of the candidate compound is warranted.


Assuntos
Bases de Dados Genéticas , Descoberta de Drogas/métodos , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/genética , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas
4.
Biomed Pharmacother ; 120: 109486, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586901

RESUMO

Osteonecrosis of the femoral head (ONFH) is usually caused by chronic and excessive alcohol dependency, and this condition largely suppresses the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). As a trimethyl derivative of glycine, betaine is an important human nutrient that regulates a series of vital biological processes, including oxidative stress, inflammatory responses, osteoblast differentiation and cellular apoptosis. However, no study has investigated the role of betaine in alcohol-induced ONFH. In this study, we hypothesized that betaine might have protective effects on ethanol-treated BMSCs and decrease the morbidity of alcohol-induced ONFH in a rat model. In vitro, we found that ethanol significantly downregulated the expression of osteocalcin (OCN), collagen 1 (COL1) and RUNX2 via activating the mammalian target of rapamycin (mTOR) signaling cascade. However, the inhibitory effects were rescued by betaine co-treatment at concentrations of 1 mM and 10 mM. In vivo, the typical ONFH pathological changes in a rat model of alcohol-induced ONFH were investigated by using multiple methods, including hematoxylin-eosin staining, micro-CT scans, TdT-mediated dUTP nick end labeling (TUNEL) assays and immunohistochemical staining for OCN and COL1. Osteonecrotic lesions of the femoral head could be alleviated by betaine as evidenced by significant histological and radiological improvements. Collectively, betaine plays a protective role against ethanol-induced suppression of osteogenesis and mineralization of hBMSCs and is thus a potential pharmacotherapy for alcohol-induced ONFH in vivo.


Assuntos
Betaína/farmacologia , Etanol/farmacologia , Cabeça do Fêmur/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/efeitos dos fármacos , Osteocalcina/metabolismo , Ratos , Ratos Sprague-Dawley
5.
BMJ Case Rep ; 12(9)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31537587

RESUMO

We describe an 11-year prospective clinical and radiologic course of a 6-year-old boy with bilateral Legg-Calvé-Perthes disease, who was treated with intravenous pamidronate (IV-PAM). His baseline radiographs showed grade IV avascular necrosis/Catterall stage IV, and at worst he progressed to lateral pillar/Herring stage C bilaterally. His disease initially was extremely functionally limiting with expected poor outcome with eventual joint replacement. Because IV-PAM stops bone breakdown and allows for ongoing bone formation while revascularisation of bone occurs, we hypothesised that IV-PAM could act as an adjunct to traditional treatment to help heal the femoral heads. Our patient received nine once monthly doses of IV-PAM (1 mg/kg/dose) over 13 months, along with Petrie/broomstick casts and physiotherapy. Remarkably, over time, his femoral heads healed. Now, at 11-year follow-up, he has excellent functional and radiologic outcome with congruence between femoral head and acetabulum, no residual osteonecrosis and minimal loss of femoral head sphericity.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Necrose da Cabeça do Fêmur/tratamento farmacológico , Doença de Legg-Calve-Perthes/tratamento farmacológico , Pamidronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Moldes Cirúrgicos , Criança , Cabeça do Fêmur/efeitos dos fármacos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/patologia , Humanos , Doença de Legg-Calve-Perthes/reabilitação , Doença de Legg-Calve-Perthes/cirurgia , Masculino , Pamidronato/administração & dosagem , Tenotomia/métodos , Resultado do Tratamento
6.
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
7.
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
8.
Orthop Clin North Am ; 50(2): 139-149, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30850073

RESUMO

Osteonecrosis of the femoral head most commonly arises from trauma or corticosteroid and alcohol use but is also associated with blood dyscrasias and metabolic and coagulation disorders. Initial evaluation includes a history and physical examination and plain radiographs. Early-stage osteonecrosis is best evaluated by MRI. The Ficat and Arlet classification system is the most widely used. Nonoperative treatment has been studied using bisphosphonates, anticoagulants, vasodilators, statins, and biophysical modalities. Operative treatment includes core decompression with or without adjuvants, such as autologous bone marrow, whereas total hip arthroplasty is reserved for advanced-stage osteonecrosis in older patients or those who have failed joint-preserving treatment.


Assuntos
Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/etiologia , Cabeça do Fêmur/diagnóstico por imagem , Corticosteroides/efeitos adversos , Artroplastia de Quadril/métodos , Transplante de Medula Óssea/métodos , Descompressão Cirúrgica/métodos , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/cirurgia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Paraproteinemias/complicações , Radiografia/métodos , Fatores de Risco , Resultado do Tratamento
9.
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
10.
Biochem Biophys Res Commun ; 508(1): 25-30, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30470573

RESUMO

BACKGROUND: HA modified by bisphosphonate (BP) (HA-BP) was synthesized by chemical reaction and possessed promising properties such as self-healing, injection ability, and strong adhesion. The main aim of this study was to confirm its role in promoting osteogenic differentiation in vitro and bone regeneration in vivo. METHODS: The cell biocompatibility of this material was determined using the CCK-8 assay. Alkaline phosphatase (ALP), osteocalcin (OT), vascular endothelial growth factor (VEGF), and collagen I were assessed by quantitative real-time polymerase chain reaction (Q-PCR) in the treated group. The number and density of calcium nodules and ALP were evaluated by Alizarin Red staining and ALP staining. We have successfully developed an animal model simulating osteonecrosis of the femoral head (ONFH). Utilizing this animal model, the impact of HA-BP/CaP on bone formation was assessed. The amount of bone regeneration at 1 and 2 months after HA-BP/CaP injection was estimated by micro-computed tomography (micro-CT) analysis and H&E, collagen I, and periostin staining. RESULTS: The number of cells gradually increased in the experimental group over time and was close to that of the blank control group. ALP, collagen I, and VEGF expression was significantly higher in the experimental group than in the blank group (VEGF, ALP, both **p < 0.01; collagen I, ***p<0.001). In addition, the number and density of calcium nodules and ALP was clearly greater in the material group than in the control group. The quantification analysis showed that the mineral contents of regenerated bone at 1 and 2 months after HA-BP/CaP injection were significantly greater than those in the control group, according to micro-CT evaluation (**p<0.01). The amount of organic components in the HA-BP/CaP group was greater than that in the control group after decalcification and H&E staining. In addition, collagen I and periostin staining further confirmed the results of H&E staining. CONCLUSION: This material can boost proliferation and osteogenic differentiation of MC3T3-E1 cells in vitro. It can intensely accelerate bone regeneration in vivo, which is a promising strategy for tissue engineering.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Necrose da Cabeça do Fêmur/tratamento farmacológico , Ácido Hialurônico/análogos & derivados , Células 3T3 , Animais , Materiais Biocompatíveis/administração & dosagem , Fosfatos de Cálcio/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colecistocinina/metabolismo , Difosfonatos/administração & dosagem , Modelos Animais de Doenças , Feminino , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/fisiopatologia , Humanos , Ácido Hialurônico/administração & dosagem , Hidrogéis , Teste de Materiais , Camundongos , Osteogênese/efeitos dos fármacos , Fragmentos de Peptídeos/metabolismo , Coelhos , Engenharia Tecidual , Microtomografia por Raio-X
11.
Int J Biol Macromol ; 123: 581-586, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30419325

RESUMO

A water-soluble polysaccharide (SPS) was purified from dried safflower (Carthamus tinctorius L.) and its structure was identified using a combination of chemical and instrumental analysis. SPS has a repeating backbone of 1,4,6-ß-Glcp, which was attached with T-ß-Glcp at its C6 position along the main chain in the molar ratio of 1:1. A steroid-induced avascular necrosis of the femoral head (SANFH) model was established in mice injected with dexamethasone (50 mg/kg) twice per week for 6 weeks. Following SPS treatment at 25 and 100 mg/kg for 60 days, the decreased bone mineral density, abnormal histopathological changes, the increased rate of empty lacunae and apoptosis rate of osteocytes of femoral head in mice induced by dexamethasone was significantly reversed. Meanwhile, increased serum hydroxyproline (HOP) and decreased serum hexosamine (HOM) concentration in mice were turned to the opposite trend with increasing dosage of SPS, thus leading to a high rate of HOM/HOP. In conclusion, SPS may serve as a potential agent for the treatment of SANFH.


Assuntos
Carthamus tinctorius/química , Necrose da Cabeça do Fêmur/tratamento farmacológico , Polissacarídeos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Modelos Animais de Doenças , Necrose da Cabeça do Fêmur/sangue , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/fisiopatologia , Hexosaminas/sangue , Humanos , Hidroxiprolina/sangue , Camundongos , Osteócitos/efeitos dos fármacos , Osteócitos/patologia , Polissacarídeos/química , Ratos , Esteroides/toxicidade
12.
J Biochem Mol Toxicol ; 33(4): e22265, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30506661

RESUMO

Steroid-induced avascular necrosis of the femoral head (SANFH) is mainly induced by glucocorticoids. Fludarabine (Flu) is a specific signal transducer and activator of transcription 1 (STAT1) inhibitor. In this study, we investigated the effect of Flu on SANFH and the role played by the STAT1/caspase-3 signaling pathway. Sprague-Dawley rats were divided into control, SANFH, and Flu-treated SANFH groups. Femoral head tissues were collected for hematoxylin-eosin (H&E) staining and Western blot analysis. The latter was used to measure the levels of stat1, phospho-stat1, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, Bax, cytochrome C, Bak, B-cell lymphoma-extra large, and B-cell lymphoma-2 protein expression. The results showed that Flu regulates protein expression in dexamethasone (Dex)-induced SANFH. H&E staining showed a decrease in the ratio of empty lacunae induced by Dex. Taken together, our study demonstrated the involvement of the STAT1/caspase-3 signaling pathway in SANFH and the potential of Flu as a therapeutic agent for patients with SANFH.


Assuntos
Caspase 3/metabolismo , Dexametasona/efeitos adversos , Regulação para Baixo/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Vidarabina/análogos & derivados , Animais , Modelos Animais de Doenças , Progressão da Doença , Cabeça do Fêmur/enzimologia , Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/tratamento farmacológico , Masculino , Ratos Sprague-Dawley , Vidarabina/farmacologia , Vidarabina/uso terapêutico
13.
Cell Physiol Biochem ; 51(1): 31-45, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30439702

RESUMO

BACKGROUND/AIMS: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. MATERIALS: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. RESULTS: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. CONCLUSION: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.


Assuntos
Dexametasona/farmacologia , RNA Longo não Codificante/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Células Cultivadas , Dexametasona/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/patologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Proteína Fosfatase 2C/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 32(11): 1421-1428, 2018 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-30417618

RESUMO

Objective: To investigate the possibility of mitochondria-dependent apoptosis as a mechanism of early steroid-induced avascular necrosis of femoral head (SANFH) in rats and vitamin E as a possible prevention strategy. Methods: Seventy-two male Sprague Dawley rats were randomly divided into control group, model group, and intervention group, with 24 rats in each group. The rats in control group were not treated as normal control. The rats in model group and intervention group were established early SANFH models by lipopolysaccharide combined with methylprednisolone injection. At the same time, the rats in intervention group were injected with vitamin E (40 mg/kg) every day for 7 days. At 2, 4, and 8 weeks after the final injection, the bilateral femoral heads were harvested and observed by HE staining, TUNEL assay, immunohistochemical staining, and Western blot. The rate of empty lacunae, apoptotic index, and the expressions of Caspase-9, Caspase-3, and cytochrome-c (Cyt-c) proteins were calculated. Results: According to histological staining, there were significant differences in the rate of empty lacunae between intervention group and control group at 8 weeks ( P<0.05) and between intervention group and model group at 4 and 8 weeks ( P<0.05). The apoptotic index of intervention group was significantly lower than that of model group at each time point ( P<0.05). And there was significant difference between the intervention group and the control group at 8 weeks ( P<0.05). According to immunohistochemistry staining and Western blot, the expressions of Cyt-c, Caspase-9, and Caspase-3 all significantly decreased in intervention group than those in model group at each time point ( P<0.05); and the differences were significant between intervention group and control group at 8 weeks ( P<0.05). Conclusion: Vitamin E can delay the progression of early SANFH by reducing mitochondrial dependent osteocyte apoptosis.


Assuntos
Necrose da Cabeça do Fêmur , Vitamina E , Vitaminas , Animais , Apoptose , Modelos Animais de Doenças , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/tratamento farmacológico , Glucocorticoides/efeitos adversos , Masculino , Metilprednisolona/efeitos adversos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Vitamina E/farmacologia , Vitaminas/farmacologia
15.
Medicine (Baltimore) ; 97(41): e12674, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30313059

RESUMO

The aim of this study was to evaluate the clinical effect of core decompression (CD), lesion clearance, and bone graft in combination with Tongluo Shenggu decoction for the treatment of osteonecrosis of the femoral head (ONFH).A total of 75 patients (92 hips), with ONFH at Association Research Circulation Osseous (ARCO) stages II to IIIA, were studied and divided into treatment group and control group. In control group, patients were treated with the CD in combination with autologous or artificial ceramic bone graft. In treatment group, patients were treated with the above method combined with Tongluo Shenggu decoction. Patients were followed-up at 1 month, 6 months, and 24 months after surgery. The visual analogue scale (VAS) scores, Harris Hip Score (HSS), and total effective rates were measured and recorded.The total effective rate of the treatment group was significantly higher than that of the control group (97.2% vs. 89.9%, P < .05). Compared with preoperative, the VAS and HSS scores were both improved at final follow-up, and there was significant difference between 2 groups (P < .01).The combination of CD, lesion clearance, and the bone graft with Tongluo Shenggu decoction is safe and effective for the treatment of ONFH, owing to which it can provide higher postoperative functional outcomes, reduce pain, and achieve smaller osteonecrosis area and better bone changes.


Assuntos
Transplante Ósseo/métodos , Descompressão Cirúrgica/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/cirurgia , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Cuidados Pós-Operatórios , Período Pós-Operatório , Estudos Retrospectivos , Índice de Gravidade de Doença
16.
J Glob Oncol ; 4: 1-11, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30241233

RESUMO

PURPOSE: With improved survival after chemotherapy for acute lymphoblastic leukemia (ALL), it is imperative to maintain good quality of life as part of the management of post-therapy adverse effects. Avascular necrosis of the femoral head (AVNFH) is one such adverse effect. A need exists for a therapy that ameliorates discomfort, provides a productive life, is cost effective, and is joint preservative. We conducted the current study to evaluate the response to bisphosphonate in the nonsurgical management of AVNFH in adolescents and young adults (AYA) who receive treatment for ALL. MATERIALS AND METHODS: This is a retrospective study of 20 AYA patients-34 affected hips-who received zolendronic acid 5 mg intravenously each year along with oral alendronate 70 mg weekly for 3 years. Clinical evaluation was performed by using the Visual Analog Scale and the Harris Hip Score. Radiographs were used to classify the Ficat-Arlet stage, monitor radiologic collapse, and evaluate the rate of progression. RESULTS: Pain relief with a drop in the Visual Analog Scale score was observed at a mean duration of 5.2 weeks (range, 3 weeks to 11 weeks) after the start of therapy. Radiologic progression by one grade was observed in 12 hips (35.3%), and only one hip (2.94%) showed progression by two grades. At a mean follow-up of 50.3 months, 31 affected hips (91.1%) had a satisfactory clinical outcome and had not required any surgical intervention. The proportion of hips that required total hip arthroplasty were 0%, 5%, and 22.2% in Ficat-Arlet stage I, II, and III, respectively. CONCLUSION: The combination of intravenous zolendronic acid and oral alendronate provides a pragmatic solution for the management of AVNFH after therapy for ALL in AYA patients. This therapy is safe, effective, and well tolerated.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Necrose da Cabeça do Fêmur/tratamento farmacológico , Adolescente , Adulto , Conservadores da Densidade Óssea/farmacologia , Terapia Combinada , Difosfonatos/farmacologia , Feminino , Necrose da Cabeça do Fêmur/patologia , Humanos , Índia , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
Bosn J Basic Med Sci ; 18(4): 352-360, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29924961

RESUMO

Angiogenic effects of epidermal growth factor (EGF), a potent mitogen, have been demonstrated previously. Moreover, different in vitro studies showed that EGF affects processes associated with bone healing, such as osteoblast differentiation and bone resorption. The aim of this study was to investigate the effect of combined core decompression (CD) and recombinant human EGF (rhEGF) treatment on early-stage osteonecrosis of the femoral head (ONFH) surgically induced in rats. ONFH was induced by dissecting the cervical periosteum and placing a ligature tightly around the femoral neck. Thirty rats were assigned to one of the following groups (n = 10 each group): sham-operated control, CD, and CD+rhEGF group. rhEGF was injected intraosseously into infarcted areas 2 weeks after the surgery. Preservation of femoral head architecture was assessed at 8 weeks post treatment by radiographic and histomorphological analyses. Osteopontin (OPN) and cluster of differentiation 31 (CD31) were detected by immunochemistry, as indicators of bone remodeling and vascular density, respectively. Inter- and intra-group (non-operated left and operated right femur) differences in radiographic and histomorphological results were analyzed. The femoral head area and sphericity were more preserved in CD+rhEGF compared to CD and sham-control group. CD31 levels were significantly different between the three groups, and were higher in CD+rhEGF compared to CD group. OPN levels were increased in CD and CD+rhEGF groups compared to sham control, but with no significant difference between CD and CD+rhEGF groups. Overall, our results indicate that EGF promotes bone formation and microvascularization in ONFH and thus positively affects the preservation of femoral head during healing.


Assuntos
Fator de Crescimento Epidérmico/uso terapêutico , Necrose da Cabeça do Fêmur/tratamento farmacológico , Necrose da Cabeça do Fêmur/etiologia , Cabeça do Fêmur/patologia , Complicações Pós-Operatórias/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Indutores da Angiogênese/uso terapêutico , Animais , Remodelação Óssea , Fator de Crescimento Epidérmico/administração & dosagem , Necrose da Cabeça do Fêmur/patologia , Infusões Intraósseas , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Osteopontina/biossíntese , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Complicações Pós-Operatórias/patologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/uso terapêutico
18.
Biomed Res Int ; 2018: 5692735, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29750162

RESUMO

Avascular necrosis of the femoral head (ANFH) is an a frequently occurring orthopaedic disease with high morbidity. Traditional Chinese Medicine (TCM) Yuanshi Shengmai Chenggu Tablet is a valid prescription for treating steroid-induced femoral head necrosis. However, there are rare investigations about the serum protein marker expression after the acting of drugs on hormone and TCM. In the present study, we aimed to systematically discover and validate the serum biomarkers expression difference in patients with steroid-induced avascular necrosis of femoral head (SANFH) after taking Yuanshi Shengmai Chenggu Tablets (SANFH-TCM), so as to reveal the action mechanism of TCM from the molecular level by using isobaric tags for relative and absolute quantification (iTRAQ) with multiple reaction monitoring quantification. Significant differences in fibrinogen alpha, fibrinogen beta, fibrinogen gamma, fibronectin, C-reactive protein, apolipoprotein A, apolipoprotein D, and apolipoprotein E were found among SANFH, SANFH-TCM, and healthy controls. Therefore, our study proposes potential biomarkers for SANFH diagnosis and for the prognosis of femoral head necrosis after Traditional Chinese Medicine treatment.


Assuntos
Biomarcadores/sangue , Proteínas Sanguíneas/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Necrose da Cabeça do Fêmur/sangue , Necrose da Cabeça do Fêmur/tratamento farmacológico , Osteonecrose/sangue , Osteonecrose/tratamento farmacológico , Comprimidos/uso terapêutico , Adulto , Feminino , Cabeça do Fêmur/efeitos dos fármacos , Cabeça do Fêmur/metabolismo , Humanos , Masculino , Medicina Tradicional Chinesa/métodos , Osteonecrose/metabolismo , Esteroides/farmacologia
19.
Int J Biol Macromol ; 116: 106-112, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29729342

RESUMO

The present study aimed to investigate the effects of a purified polysaccharide (SPS) from the safflower in a cellular model of steroid-associated necrosis of the femoral head (SANFH), which was established in primary murine osteoblasts suffering dexamethasone pretreatment. After treatment with SPS (25, 50 and 100 µg/ml), the degree of necrosis induced by dexamethasone was significantly reduced in osteoblasts as evidenced by an increase of cell viability and a decrease of apoptosis in osteoblasts. Furthermore, pretreatment with SPS (25, 50 and 100 µg/ml) significantly attenuated the activation of caspase-3 and cleavage of PARP relative to the model control cells. The addition of caspase-3 inhibitor (Z-DEVD-FMK) in dexamethasone-treated osteoblasts resulted in the inefficiency of SPS for inhibiting cellular apoptosis. Dose-dependent increases in alkaline phosphatase (ALP) activity, collagen synthesis and mineralization were also observed in SPS-treated osteoblasts at 72 h. The present study demonstrates that SPS may alleviate dexamethasone associated osteonecrosis by inhibiting caspsae-3-mediated apoptosis and may provide an alternative treatment for SANFH.


Assuntos
Apoptose/efeitos dos fármacos , Carthamus tinctorius/metabolismo , Caspase 3/metabolismo , Necrose da Cabeça do Fêmur/tratamento farmacológico , Polissacarídeos/farmacologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/farmacologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Camundongos , Osteoblastos/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Esteroides/farmacologia
20.
Int Orthop ; 42(7): 1551-1556, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29594456

RESUMO

PURPOSE: The purpose of this study was to retrospectively analyze the clinical, functional, and radiological outcomes of combined pharmacotherapy to ONFH after high-dose corticosteroid therapy. METHOD: From August 2003 to June 2015, five patients (ten hips) of ONFH in ARCO stage I, after SARS and Interstitial pneumonia, were treated by combined pharmacotherapy. Lipo-prostaglandin E1 10 µg iv Bid × 28 days, enoxaparin 6000 iu H QD × 12 weeks, alendronate sodium tablet 10 mg QD × 1 year. The patients were fully weight-bearing following completion of the follow-up. RESULT: For these five patients (ten hips), Harris score was 100 from the diagnosis to final follow-up time. Radiologic findings show no signs of collapse, necrotic focus was repaired, and ARCO stages were changed from IC into IIB. CONCLUSION: This combined pharmacotherapy has promising treatment results for delaying or preventing collapse of ONFH in ARCO stage I.


Assuntos
Alendronato/administração & dosagem , Alprostadil/administração & dosagem , Enoxaparina/administração & dosagem , Necrose da Cabeça do Fêmur/tratamento farmacológico , Doenças Pulmonares Intersticiais/complicações , Síndrome Respiratória Aguda Grave/complicações , Adulto , Conservadores da Densidade Óssea/administração & dosagem , Quimioterapia Combinada , Feminino , Necrose da Cabeça do Fêmur/etiologia , Fibrinolíticos/administração & dosagem , Seguimentos , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
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