RESUMEN
PURPOSE: Increasing evidences suggest dysfunctions of microRNAs (miRNAs) are playing important part in tumors. Therefore, the role of miR-802 in osteosarcoma (OS) was exploited. The object was to evaluate the effect of miR-802 and verify its influence on p27 Kip1 (p27) in OS. METHODS: RT-qPCR experiment was used to detect miR-802 and p27 expression in OS tissues and cells. We explored the function of miR-802 through Transwell assays. The phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathway and epithelial-mesenchymal transition (EMT) was detected by Western blot assays. Luciferase assay was used to testify the target of miR-802. RESULTS: MiR-802 expression was elevated in OS, which was related to poor clinical outcome in OS patients. MiR-802 overexpression promoted OS migration, invasion and EMT. Further, p27 is a direct target of miR-802. P27 elevation counteracted the promotion effect of OS on EMT, migration and invasion induced by miR-802. In addition, miR-802 overexpression inactivated PI3K/AKT pathway via targeting p27 in OS. CONCLUSION: MiR-802 promoted the progress of EMT, migration and invasion in OS via targeting p27. This newly identified miR-802/p27/PI3K/AKT axis may represent potential targets for OS.
Asunto(s)
Neoplasias Óseas/etiología , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/fisiología , MicroARNs/fisiología , Osteosarcoma/etiología , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Adolescente , Neoplasias Óseas/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Osteosarcoma/patología , Adulto JovenRESUMEN
MicroRNAs (miRNAs) are a class of small (20-24 nucleotides), highly conserved, non-coding RNA molecules whose main function is the post-transcriptional regulation of gene expression through sequence-specific manners, such as mRNA degradation or translational repression. Since these key regulatory molecules are implicated in several biological processes, their altered expression affects the preservation of cellular homeostasis and leads to the development of a wide range of pathologies. Over the last few years, relevant investigations have elucidated that miRNAs participate in different stages of bone growth and development. Moreover, the abnormal expression of these RNA molecules in bone cells and tissues has been significantly associated with the progression of numerous bone diseases, including osteoporosis, osteosarcoma, osteonecrosis and bone metastasis, among others. In fact, miRNAs regulate multiple pathological mechanisms, including altering either osteogenic or osteoblast differentiation, metastasis, osteosarcoma cell proliferation, and bone loss. Therefore, in this present review, aiming to impulse the research arena of the biological implications of miRNA transcriptome in bone diseases and to explore their potentiality as a theragnostic target, we summarize the recent findings associated with the clinical significance of miRNAs in these ailments.
Asunto(s)
Biomarcadores , Enfermedades Óseas/etiología , Enfermedades Óseas/terapia , Susceptibilidad a Enfermedades , Regulación de la Expresión Génica , MicroARNs/genética , Interferencia de ARN , Animales , Enfermedades Óseas/metabolismo , Enfermedades Óseas/patología , Manejo de la Enfermedad , Exosomas , Humanos , Metástasis de la Neoplasia , Osteogénesis/genética , Osteonecrosis/etiología , Osteonecrosis/metabolismo , Osteonecrosis/patología , Osteoporosis/genética , Osteoporosis/metabolismo , Osteoporosis/patología , Osteosarcoma/etiología , Osteosarcoma/metabolismo , Osteosarcoma/patología , Transporte de ARN , Transducción de SeñalRESUMEN
La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son caracteriÌsticos, aunque variables y de caraÌcter evolutivo. La gammagrafiÌa ósea es la teÌcnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnoÌstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)
Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)
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Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Adulto Joven , Displasia Fibrosa Ósea/etiología , Displasia Fibrosa Ósea/tratamiento farmacológico , Osteogénesis/genética , Osteomalacia/complicaciones , Anomalías Congénitas , Vitamina D/uso terapéutico , Osteosarcoma/etiología , Calcio/uso terapéutico , Hipofosfatemia/sangre , Quistes Óseos Aneurismáticos/etiología , Diagnóstico Diferencial , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Fracturas Óseas/patología , Células Madre Mesenquimatosas/patología , Manejo del Dolor , Displasia Fibrosa Monostótica/etiología , Displasia Fibrosa Ósea/genética , Displasia Fibrosa Ósea/sangre , Displasia Fibrosa Ósea/diagnóstico por imagen , Displasia Fibrosa Poliostótica/etiología , Displasia Fibrosa Poliostótica/diagnóstico por imagen , Displasia Fibrosa Craneofacial/etiología , Mutación/genéticaRESUMEN
The discovery of biomaterials led to their use in the manufacture of implants for biomedical applications. In vivo, no metal or alloy is completely inert. The potential toxicity of some of the metals most frequently employed in the manufacture of orthopedic implants has been reported. Their carcinogenic potential has been evaluated in experimental animal models. However, few reports have discussed the potential development of malignant tumors associated with prosthetic structures in humans. The present study documents a case of intraosseous sarcoma that developed in the vicinity of a metallic prosthesis 43 months after a coxofemoral arthrodesis with metallic pins and screws. With this report the authors seek to contribute to the understanding of the potential toxicity and risks of using metallic implants. Since metallic implants employed in the rehabilitation of osteo-muscular-articular disorders usually remain in the organism for long periods of time, the need to monitor the metallic structures and the adjacent tissues is extremely relevant.
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Artrodesis/efectos adversos , Fracturas del Fémur/cirugía , Histiocitoma Fibroso Benigno/etiología , Metales/efectos adversos , Osteosarcoma/etiología , Adulto , Femenino , Histiocitoma Fibroso Benigno/patología , Humanos , Osteosarcoma/patologíaRESUMEN
A 72-yr-old acromegalic man, who presented with pain in the left femur, was found to have a metastatic osteosarcoma. Only three cases describing the coexistence of acromegaly and osteosarcoma have been reported by the literature. As the patient didn't have other risk factors for osteosarcoma, the hypothesis that accelerated rate of bone turnover caused by long-term exposure to high GH and IGF-I could act as a predisposing factor in the development of this malignant bone tumor is discussed.
Asunto(s)
Acromegalia/complicaciones , Neoplasias Femorales/etiología , Osteosarcoma/etiología , Anciano , Neoplasias Óseas/secundario , Resultado Fatal , Humanos , Masculino , Osteosarcoma/secundarioRESUMEN
La transformación sarcomatosa de la displasia fibrosa ha sido reportada en pacientes con y sin antecedentes de tratamientos radiantes, el primer caso documentado y comunicado es del año 1945 por Coley y Stewart. La incidencia actualmente más aceptada es del 0,5 por ciento en las formas monostóticas y del 4 por ciento en las poliostóticas (síndrome de Albrigth). El motivo de ésta presentación es la comunicación de ésta entidad en un paciente de 55 años con antecedentes de displasia fibrosa poliostótica de varios años de evolución (AU)