RESUMO
Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells that are formed by mononuclear preosteoclast fusion. Fat-soluble vitamins such as vitamin D are pivotal in maintaining skeletal integrity. However, the role of vitamin E in bone remodeling is unknown. Here, we show that mice deficient in α-tocopherol transfer protein (Ttpa(-/-) mice), a mouse model of genetic vitamin E deficiency, have high bone mass as a result of a decrease in bone resorption. Cell-based assays indicated that α-tocopherol stimulated osteoclast fusion, independent of its antioxidant capacity, by inducing the expression of dendritic-cell-specific transmembrane protein, an essential molecule for osteoclast fusion, through activation of mitogen-activated protein kinase 14 (p38) and microphthalmia-associated transcription factor, as well as its direct recruitment to the Tm7sf4 (a gene encoding DC-STAMP) promoter. Indeed, the bone abnormality seen in Ttpa(-/-) mice was rescued by a Tm7sf4 transgene. Moreover, wild-type mice or rats fed an α-tocopherol-supplemented diet, which contains a comparable amount of α-tocopherol to supplements consumed by many people, lost bone mass. These results show that serum vitamin E is a determinant of bone mass through its regulation of osteoclast fusion.
Assuntos
Reabsorção Óssea/dietoterapia , Osso e Ossos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Deficiência de Vitamina E/patologia , Vitamina E/administração & dosagem , Vitaminas/administração & dosagem , Aminoácidos/sangue , Animais , Apoptose/efeitos dos fármacos , Reabsorção Óssea/etiologia , Reabsorção Óssea/genética , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Bromodesoxiuridina/metabolismo , Proteínas de Transporte/genética , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Imunoprecipitação da Cromatina , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Marcação In Situ das Extremidades Cortadas , Fator Estimulador de Colônias de Macrófagos/metabolismo , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Transcrição Associado à Microftalmia/metabolismo , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Nitrofenóis/metabolismo , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Ligante RANK/metabolismo , RNA Interferente Pequeno/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tomografia Computadorizada por Raios X , Transfecção , Vitamina E/sangue , Deficiência de Vitamina E/complicações , Deficiência de Vitamina E/dietoterapia , Deficiência de Vitamina E/genética , Vitaminas/sangue , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/sangueRESUMO
Bridge grafting (15 mm) into the sciatic nerve of SD rats was carried out using tendon chitosan tubes having either a circular or triangular cross-section, as well as triangular tubes combined with laminin, CDPGYIGSR, or CSRARKQAASIKVAVSAD (n = 15 in each group). As a control, isografting (15 mm) was carried out in the SD rats (n = 7). Specimens were taken after 1, 2, 4, 6, and 8 weeks for histology, and nerve regeneration was evaluated electro-physiologically and histologically after 12 weeks. The mechanical strength of triangular tubes was found to be higher than circular tubes, and the inner volume of a triangular tube tends to be larger than in circular tubes. Nerve tissue regeneration along the tube wall was found in both the laminin and laminin peptide groups. According to the result of percentage neural tissue in relation to evoked action potentials, the consecutive treatments of YIGSR and IKVAV was found to match the effectiveness of intact laminin.