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1.
Biomed Res Int ; 2021: 6655225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928159

RESUMO

Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.


Assuntos
Exossomos/metabolismo , Necrose da Cabeça do Fêmur/prevenção & controle , Necrose da Cabeça do Fêmur/terapia , Cabeça do Fêmur/irrigação sanguínea , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica , Esteroides/efeitos adversos , Animais , Osso e Ossos/patologia , Hipóxia Celular , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Exossomos/ultraestrutura , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ratos Sprague-Dawley , Microtomografia por Raio-X
2.
Drug Des Devel Ther ; 15: 983-995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692615

RESUMO

Summary: The recent outbreak of coronavirus disease 2019 (COVID-19) has become a global epidemic. Corticosteroids have been widely used in the treatment of severe acute respiratory syndrome (SARS), and the pathological findings seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are very similar to those observed in severe acute respiratory syndrome-related coronavirus (SARS-CoV) infection. However, the long-term use of corticosteroids (especially at high doses) is associated with potentially serious adverse events, particularly steroid-induced avascular necrosis of the femoral head (SANFH). In today's global outbreak, whether corticosteroid therapy should be used, the dosage and duration of treatment, and ways for the prevention, early detection, and timely intervention of SANFH are some important issues that need to be addressed. This review aims to provide a reference for health care providers in COVID-19 endemic countries and regions. Article Focus: Hormones are a double-edged sword. This review aims to provide a reference for health care providers in coronavirus disease 2019 (COVID-19) endemic countries and regions, especially with respect to the pros and cons of corticosteroid use in the treatment of patients with COVID-19. Key Messages: In today's global outbreak, whether corticosteroid therapy should be used, the dosage and duration of treatment, and ways for the prevention, early detection, and timely intervention of SANFH are some important issues that need to be addressed. Strengths and Limitations: Since SARS was mainly prevalent in China at that time, many evidences in this paper came from the reports of Chinese scholars. There is a bias in the selection of data, which may ignore the differences in environment, race, living habits, medical level and so on. SANFH may be the result of multiple factors. Whether the virus itself is an independent risk factor for SANFH has not been confirmed. In this paper, through literature retrieval, some reference opinions on glucocorticoid usage, diagnosis and treatment of SANFH are given. However, due to the lack of large-scale research data support, it can not be used as the gold standard for the above problems.


Assuntos
Corticosteroides/efeitos adversos , Necrose da Cabeça do Fêmur/induzido quimicamente , Adulto , Idoso , Animais , Tomada de Decisão Clínica , Feminino , Necrose da Cabeça do Fêmur/diagnóstico , Necrose da Cabeça do Fêmur/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Medição de Risco , Fatores de Risco , Resultado do Tratamento
3.
Int Immunopharmacol ; 93: 107345, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33563553

RESUMO

Osteonecrosis of the femoral head (ON-FH) is a common complication of steroid use. Pro-inflammatory macrophages play a crucial role in the apoptosis of osteocytes. The objective of the study was to evaluate a plant extract astragaloside IV (AS-IV) in treating ON-FN. Bone-marrow-derived macrophages (BMDMs) were treated with lipopolysaccharides (LPS), IFN-γ or IL-4 to induce M1 and M2-like phenotypes. Quantitative real-time PCR and Western blot were used to examine M1 and M2 phenotypic markers. Flow cytometry was used to analyze MHC II, CD206, F4/80, and CD11b levels and cell apoptosis. Glucocorticoid was used to induce ON-FN in mice. TNF-α and IL-1ß levels in femoral head were determined using enzyme-linked immunosorbent assay. AS-IV repolarized macrophages from M1 to M2 phenotypes. Culture medium from AS-IV treated M1 macrophages induced less cell apoptosis osteocytes compared to that from untreated M1 macrophages. In ON-FH mice, the ratio of M1 macrophages was decreased in the femoral head by AS-IV, concomitant with a decrease in TNF-α and IL-1ß levels. AS-IV is effective in alleviating ON-FH through its effects in repolarizing macrophages from M1-like phenotype to M2-like phenotype, promoting survival of osteocytes, reducing arthritic symptoms, and decreasing inflammatory cytokines.


Assuntos
Necrose da Cabeça do Fêmur/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Animais , Células Cultivadas , Feminino , Cabeça do Fêmur/efeitos dos fármacos , Cabeça do Fêmur/imunologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/imunologia , Glucocorticoides , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Fenótipo , Saponinas/farmacologia , Triterpenos/farmacologia
4.
Gene ; 766: 145128, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32911026

RESUMO

BACKGROUND: The pathogenesis of osteonecrosis of the femoral head (ONFH) is unclear. Our previous study demonstrated that upregulated miR-335 in bone microvascular endothelial cells (BMECs) might be associated with the disease of steroid-induced ONFH. Here, we study the preventive effect of ICA on steroid-induced ONFH in rats. METHOD: 90 rats were separated into three groups: control group, methylprednisolone (MPS) group, and MPS + Icariin (ICA) group. Four weeks later, histological analyses were performed. Thrombomodulin (TM) and vascular endothelial growth factor (VEGF) were tested. MiRNA-335 expression was screened in the three groups using Agilent Gene Spring GX software. Target genes of miRNA-335 were detected by bioinformatics analysis. The functions of BMECs were analyzed by scratch, angiogenesis and cell survival rate. RESULTS: ICA can prevent the occurrence of steroid-associated ONFH in rats and reduce the amount of TM and VEGF in serum induced by glucocorticoids. ICA could regulate the overexpression of miRNA-335 induced by glucocorticoids. We predicted the Gene ontology (GO) and signaling pathways of target genes. At 24 hours, we found that ICA significantly promoted BMECs migration abilities. We also found that ICA could promote the angioplasty ability of BMECs. ICA could improve the survival rate of BMECs after steroid-induced injury. CONCLUSIONS: ICA is effective to prevent the occurrence of steroidinduced ONFH. ICA has a protective effect against steroid-induced BMECs injury. ICA regulated the imbalance of miRNA-335 expression induced by the glucocorticoid in BMECs, which provides a new viewpoint to explore the mechanism of ICA in preventing steroid-induced ONFH.


Assuntos
Células Endoteliais/efeitos dos fármacos , Necrose da Cabeça do Fêmur/tratamento farmacológico , Cabeça do Fêmur/efeitos dos fármacos , Flavonoides/farmacologia , MicroRNAs/metabolismo , Neovascularização Patológica/tratamento farmacológico , Substâncias Protetoras/farmacologia , Adipogenia/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Glucocorticoides/metabolismo , Metilprednisolona/farmacologia , Neovascularização Patológica/metabolismo , Osteócitos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Esteroides/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Jt Dis Relat Surg ; 31(2): 390-394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584743

RESUMO

Osteonecrosis, commonly known as avascular necrosis (AVN) of bone, is one of the universally recognized side effects of high-dose steroids and commonly involves femur head leading to significant morbidity. However, the development of AVN in the femoral head due to low-dose oral corticosteroid therapy in a short time is a rare occurrence. Management by stopping corticosteroid treatment can be challenging in many cases due to the adrenal crisis. Glucocorticoids may have to be continued in the lowest possible dose using a physiological preparation, such as hydrocortisone, when the stoppage is not possible. In this article, we report a 34-year-old male patient with hypopituitarism who developed bilateral AVN while receiving a mild physiological replacement oral prednisolone dose for only three years for secondary adrenal insufficiency of hypopituitarism after transsphenoidal surgery. The patient was switched to hydrocortisone and underwent core decompressive surgery resulting in a reduction of hip pain and improvement. The case report intends to highlight the occurrence of AVN of the femur even with a very low dose of corticosteroid used for the treatment of panhypopituitarism. Avascular necrosis should be considered in the differential diagnosis in patients with hip pain, even in low-dose steroid use because early diagnosis is essential to prevent progression, collapse, and eventually the need for hip replacement in AVN.


Assuntos
Descompressão Cirúrgica/métodos , Necrose da Cabeça do Fêmur , Hipopituitarismo , Prednisolona , Adulto , Diagnóstico Diferencial , Relação Dose-Resposta a Droga , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/diagnóstico , Necrose da Cabeça do Fêmur/terapia , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hipopituitarismo/tratamento farmacológico , Hipopituitarismo/etiologia , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Resultado do Tratamento
6.
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
7.
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 , Imageamento 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
8.
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
9.
Carbohydr Polym ; 233: 115856, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32059907

RESUMO

A water-soluble polysaccharide (SPAW) was purified from Safflower and it was identified to be (1→3)-linked ß-d-Glucan. The therapeutic effect and underlying mechanism of SPAW on steroid-induced avascular necrosis of the femoral head (SANFH) in a rabbit model was performed here. The abnormal histopathologic changes and apoptosis of femoral head in model group were significantly reverted after SPAW (25, 100 and 200 mg/kg) administration for 60 days, as evidenced by the a decline of empty lacunae rate, the average bone marrow fat cell size and the proportion of apoptotic cells. Furthermore, administration of SPAW significantly decreased the Bax and caspase-3 protein expression, but increased the protein expression of Bcl-2 when compared these in model rabbits. Meanwhile, increased hydroxyproline (HOP) and decreased serum hexosamine (HOM) concentration in rabbit serum were turned to the opposite way. The present study suggested that SPAW may provide an alternative treatment for the treatment of SANFH.


Assuntos
Carthamus tinctorius/química , Necrose da Cabeça do Fêmur/tratamento farmacológico , Glucanos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Feminino , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Glucanos/química , Glucanos/isolamento & purificação , Hexosaminas/metabolismo , Cavalos , Hidroxiprolina/metabolismo , Masculino , Hemissuccinato de Metilprednisolona , Peso Molecular , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Coelhos , Ratos , Proteína X Associada a bcl-2/metabolismo
10.
Eur J Orthop Surg Traumatol ; 30(2): 193-197, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31538269

RESUMO

Femoral head avascular bone necrosis (AVN) is the loss of blood supply to the bone tissue of femoral head that results in cellular death. This condition causes a significant limitation in patient daily life activities and has a poor functional outcome. Long-term steroid intake was established as a cause of AVN. However, few cases reported femoral head AVN post-single steroid intra-articular injection. We review all cases of AVN that results from single intra-articular steroid injection and present a case of femoral head AVN developed in a 78-year-old male. The patient, who was not known to have any medical illness, presented complaining of mild left hip pain for 4 months with long distant ambulation and weight standing. He was diagnosed to have left hip joint osteoarthritis for which he received intra-articular steroid injection 2 months prior visiting our orthopedics center. MRI of the pelvis revealed AVN of the femoral head. He underwent total hip arthroplasty. The pathological examination confirmed the diagnosis of AVN. To best of our knowledge, this is the fifth case of AVN of femoral head AVN after single intra-articular steroid injection. We reviewed all cases of AVN of femoral head after single steroid injection. Intra-articular steroid injection can cause femoral head AVN, and the patient receiving these injections should be aware about this rare but significant complication that results in poor functional outcome and significant morbidity.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Esteroides/efeitos adversos , Idoso , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/efeitos dos fármacos , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/patologia , Humanos , Injeções Intra-Articulares , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Esteroides/administração & dosagem
11.
J Orthop Sci ; 25(3): 466-471, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31280930

RESUMO

BACKGROUND: Immunosuppressive therapy for renal allograft recipients has changed substantially since the introduction of the anti-CD25 monoclonal antibody, basiliximab. We hypothesized that recent improvements in immunosuppressive treatment may reduce the incidence of osteonecrosis of the femoral head (ONFH). This study aimed to investigate transitional changes in the incidence of OFNH among renal transplant recipients by MRI. METHODS: Participants comprised 110 patients who had undergone renal transplantation from 2003 to 2012, during which time basiliximab was in regular use at our institute (Recent group), and 232 patients who had undergone RT between 1986 and 2003 (Past group). We compared ONFH incidence between the two groups and evaluated risk factors for ONFH, including immunosuppressants (calcineurin inhibitors, basiliximab, and/or steroids) and postoperative renal function. RESULTS: Incidence of ONFH was lower in the Recent group (0%) than in the Past group (3.4%; p = 0.043). In the Recent group, age was greater, ABO/human leukocyte antigen incompatibility was worse, while steroid dose was decreased and post-transplant renal function was improved. Cumulative methylprednisolone dose at postoperative week 2 and delayed graft function were identified as risk factors for ONFH. CONCLUSION: Risk of ONFH after renal transplantation has fallen with the advent of regular use of basiliximab, although this agent does not appear to be a factor directly associated with the incidence of ONFH. STUDY DESIGN: Clinical prognostic study (Level III case control study).


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/epidemiologia , Imunossupressores/efeitos adversos , Transplante de Rim , Adolescente , Adulto , Idoso , Feminino , Glucocorticoides/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Stem Cell Res Ther ; 10(1): 321, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730486

RESUMO

BACKGROUND: Damaged endothelial cells and downregulated osteogenic ability are two key pathogenic mechanisms of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies suggested that transplantation of CD34+ stem cell-derived exosomes (CD34+-Exos) can treat ischemic diseases by promoting neovascularization and that miR-26a is an important positive regulator of osteogenesis. Moreover, the biological effect of exosomes is closely related to their cargo miRNAs. However, it is not clear whether increasing the abundance of miR-26a in CD34+-Exos will inhibit the progress of GC-induced ONFH. METHODS: MiR-26a was overexpressed in CD34+-Exos (miR-26a-CD34+-Exos) to increase their osteogenic potential. The angiogenic potential of miR-26a-CD34+-Exos was then examined through evaluations of migration and tube-forming capacities in vitro. In addition, in order to observe the osteogenic effect of miR-26a-CD34+-Exos on bone marrow stromal cells (BMSCs), Alizarin red staining, alkaline phosphatase (ALP) activity assays, and qPCR were carried out. Finally, miR-26a-CD34+-Exos were injected into a GC-induced ONFH rat model to prevent the progress of GC-induced ONFH. The biological effects of miR-26a-CD34+-Exos on the ONFH model were evaluated by micro-CT, angiography, and histological staining. RESULTS: Our data showed that miR-26a-CD34+-Exos enhanced human umbilical vein endothelial cell migration and tube-forming capacities. Furthermore, miR-26a-CD34+-Exos strengthened the osteogenic differentiation of BMSCs under the influence of GCs in vitro. Finally, the miR-26a-CD34+-Exos increased the vessel density and trabecular bone integrity of the femoral head in the GC-induced ONFH rat model, which inhibited the progress of ONFH. CONCLUSIONS: MiR-26a-CD34+-Exos protect the femoral head from damage caused by GCs by strengthening angiogenesis and osteogenesis. The biological effect of miR-26a-CD34+-Exos make them suitable for application in the prevention of GC-induced ONFH.


Assuntos
Antígenos CD34/metabolismo , Exossomos/metabolismo , Necrose da Cabeça do Fêmur/terapia , Glucocorticoides/efeitos adversos , MicroRNAs/metabolismo , Neovascularização Fisiológica , Osteogênese , Células-Tronco/metabolismo , Animais , Movimento Celular/genética , Sobrevivência Celular/genética , Modelos Animais de Doenças , Exossomos/ultraestrutura , Feminino , Necrose da Cabeça do Fêmur/induzido quimicamente , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/genética , Ratos Sprague-Dawley , Transfecção
13.
J Cell Mol Med ; 23(11): 7320-7330, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31507078

RESUMO

The injury and dysfunction of the femoral head microvascular endothelial cells are associated with the pathogenesis of glucocorticoid-induced osteonecrosis of the femoral head (ONFH). Reports indicate that icariin (ICA) can enhance vascular roles and also inhibit endothelial cell dysfunction. However, it still remains unclear whether ICA can promote angiogenesis in glucocorticoid-induced ONFH. In this study, we investigate this hypothesis through in vitro and in vivo experiments. Results showed that 0.1 mg/mL hydrocortisone significantly suppressed bone microvascular endothelial cells (BMECs) proliferation while ICA at 10-5  mol/L reversed this inhibition. ICA significantly promoted BMECs migration, tube formation, the angiogenesis-related cytokines expression and the activation of Akt. Furthermore, ICA enhanced Bcl-2 expression but diminished Bax expression. According to in vivo results, rats with ICA treatment exhibited a lower ratio of empty lacunae, higher volume of blood vessels and more CD31-positive cells. This study revealed that ICA promotes angiogenesis of BMECs in vitro and improves femoral head blood vessel volume of rats treated with glucocorticoid, suggesting the efficacy of ICA in the prevention of glucocorticoid-induced ONFH.


Assuntos
Necrose da Cabeça do Fêmur/prevenção & controle , Flavonoides/farmacologia , Glucocorticoides/toxicidade , Neovascularização Patológica/prevenção & controle , Osteócitos/efeitos dos fármacos , Animais , Movimento Celular , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Técnicas In Vitro , Neovascularização Patológica/induzido quimicamente , Neovascularização Patológica/patologia , Osteócitos/patologia , Ratos , Ratos Sprague-Dawley
14.
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
15.
Eur Rev Med Pharmacol Sci ; 23(3 Suppl): 54-59, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31389574

RESUMO

OBJECTIVE: To explore the clinical correlation between the hsa-miR-122-3p expression in bone marrow mesenchymal stem cells (BMSCs) and steroid-induced necrosis of femoral head (SONFH). PATIENTS AND METHODS: A total of 62 SONFH patients were selected as the experimental group, while another 72 patients with femoral neck fracture (FNF) were selected as the control group. The bone marrow was obtained from patients during operation and used to culture the BMSCs. The expression of hsa-miR-122-3p in BMSCs was detected via real-time quantitative polymerase chain reaction (qPCR) in both groups. The patients in experimental group were further divided into Ficat stage III group and stage IV group according to the Ficat stage, and the expression of hsa-miR-122-3p in BMSCs was also detected via qPCR in the two groups. RESULTS: The expression level of hsa-miR-122-3p in SONFH group was significantly lower than that in FNF group, and the difference was statistically significant (p<0.05). The expression level of hsa-miR-122-3p in Ficat stage IV group was significantly lower than that in stage III group (p<0.05). CONCLUSIONS: We demonstrated that the expression of hsa-miR-122-3p in BMSCs declined in SONFH group, indicating that hsa-miR-122-3p may be involved in the regulation of the pathological process of SONFH, and the expression level of hsa-miR-122-3p in BMSCs may be correlated with the progression of SONFH.


Assuntos
Fraturas do Colo Femoral/genética , Necrose da Cabeça do Fêmur/genética , Perfilação da Expressão Gênica/métodos , MicroRNAs/genética , Esteroides/efeitos adversos , Idoso , Células Cultivadas , Regulação para Baixo , Feminino , Necrose da Cabeça do Fêmur/induzido quimicamente , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Pessoa de Meia-Idade
16.
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
17.
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
18.
Calcif Tissue Int ; 105(5): 506-517, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31359074

RESUMO

Glucocorticoid (GC)-induced osteonecrosis has been considered as the most serious side effect in long-term or over-dose steroid therapy. The decreased bone mass and increased marrow fat tissue demonstrated that GC can destroy the normal differentiation of bone marrow mesenchymal stem cells (BMSCs), which accelerates adipogenesis but not osteogenesis. However, the underlying mechanisms are still unclear. Ski, an evolutionary conserved protein, is a multifunctional transcriptional regulator that involved in regulating signaling pathways associated with adipogenesis differentiation, but the concrete function remains unclear. In this work, we first established a methylprednisolone (MPS)-induced osteonecrosis of femoral head (ONFH) rabbit model, in which the expression of Ski, PPAR-γ, and FABP4 was up-regulated compared with control group, and then we induced the isolated BMSCs from rabbit with dexamethasone (Dex) in vitro and the results showed that the Ski expression was up-regulated by Dex in a dose- and time-dependent manner. Therefore, we demonstrated that the expression of Ski was up-regulated in glucocorticoid-related osteonecrosis disease in vivo and in vitro. Moreover, the adipogenesis differentiation capacity of BMSCs was enhanced after induced by Dex, which was identified by Oil Red O staining, and the up-regulated PPAR-γ and FABP4 expression. To further study the function of Ski in BMSC after induced by Dex, Ski specific small interfering RNA (Ski-siRNA) was used. Results showed that knockdown of Ski obviously decreased adipogenesis differentiation evident by Oil Red O staining, and the expression of PPAR-γ and FABP4 was down-regulated simultaneously. Collectively, our findings suggest that Ski increased significantly during glucocorticoid-induced adipogenic differentiation of BMSCs, and the expression level was consistent with adipogenic-related proteins including PPAR-γ and FABP4. Based on the above data, we believe that Ski might become a new molecule in the treatment of GC-induced ONFH and our study could provide a basis for further study on the detailed function of Ski in ONFH.


Assuntos
Adipogenia/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/toxicidade , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Dexametasona/toxicidade , Proteínas de Ligação a Ácido Graxo/metabolismo , Necrose da Cabeça do Fêmur/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Metilprednisolona/toxicidade , PPAR gama/metabolismo , Coelhos
19.
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
20.
Eur Rev Med Pharmacol Sci ; 23(11): 4599-4608, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31210286

RESUMO

OBJECTIVE: To study the effect of micro-ribonucleic acid (miR)-20b on osteocyte apoptosis in rats with steroid-induced necrosis of the femoral head (SNFH) and to analyze whether the bone morphogenetic protein (BMP) signaling pathway is involved in the regulation. MATERIALS AND METHODS: A total of 36 Sprague-Dawley rats were randomly divided into control group (n=12), model group (n=12) and intervention group (n=12). The rat model of SNFH was established in the model and intervention groups, while the rats in the intervention group were intraperitoneally injected with the bone morphogenetic protein (BMP) signaling pathway inhibitor. After modeling, the femoral head in each group was taken, and the morphology of osteocytes was observed via hematoxylin-eosin (HE) staining. The apoptosis level of femoral head cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The miR-20b expression level in femoral head cells in each group was detected via quantitative Polymerase Chain Reaction (qPCR). The expression levels of inflammatory factors in femoral head cells in each group were detected via enzyme-linked immunosorbent assay (ELISA). The expression levels of apoptotic proteins and BMP signaling pathway-related proteins in femoral head cells in each group were detected via Western blotting. RESULTS: Compared with those in the control group, the bone trabecula was sparse, the number of osteocytes significantly declined and the number of apoptotic osteocytes markedly increased (p<0.01); the expression level of miR-20b in bone tissues remarkably increased (p<0.01), the content of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) in bone tissues increased (p<0.01), the content of IL-10 significantly declined (p<0.01), the expression level of cleaved caspase-3 protein in bone tissues markedly increased (p<0.01), the Bcl-2/Bax expression level evidently declined (p<0.01) and the expression levels of anaplastic lymphoma kinase3 (ALK3), GATA4 and NKX2.5 in bone tissues remarkably increased (p<0.01) in the model group. Compared with those in the model group, the necrosis of bone tissues significantly decreased, the apoptosis level of osteocytes remarkably declined (p<0.01), the content of IL-1ß, IL-6 and TNF-α in bone tissues markedly decreased (p<0.01), the content of IL-10 increased (p<0.01), the expression level of cleaved caspase-3 protein in bone tissues significantly declined (p<0.01), the B-cell lymphoma 2/BCL2-Associated X (Bcl-2/Bax) expression level markedly increased (p<0.01) and the expression levels of ALK3, GATA4 and NKX2.5 in bone tissues significantly decreased (p<0.01) in the intervention group. CONCLUSIONS: SNFH will significantly increase the expression level of miR-20b in bone tissues, thereby activating the BMP signaling pathway, promoting the release of inflammatory factors and leading to osteocyte apoptosis. Inhibiting the BMP signaling pathway can effectively reduce the osteocyte apoptosis level.


Assuntos
Necrose da Cabeça do Fêmur/genética , Metilprednisolona/efeitos adversos , MicroRNAs/genética , Osteócitos/citologia , Animais , Apoptose , Receptores de Proteínas Morfogenéticas Ósseas/metabolismo , Modelos Animais de Doenças , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Injeções Intraperitoneais , Osteócitos/química , Osteócitos/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
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