Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
Texto Completo: | http://repositorio.ufes.br/handle/10/1880 |
Resumo: | It is currently observed an increase in the incidence of osteometabolic diseases, particularly osteoporosis. This disease is caused by an imbalance between bone formation and bone resorption, closely linked to aging. In osteoporosis, it is observed that the predominance of bone resorption leads to a lower bone mineral density (BMD). It is believed that decrease in BMD is the main risk factor for bone breaking observed in these patients. Although low BMD represents the main risk factor for osteoporosis, this disease is multifactorial. Another remarkable feature in osteoporosis is its prevalence in postmenopausal women. It is now known that estrogen is one of the major factors responsible for the formation of bone tissue and its mineralization. Therefore, its deficiency at menopause results in a higher incidence of the disease in this population. Nevertheless studies in humans have contributed immensely to the understanding of the disease, the limitations imposed by the techniques to be used prevents the investigation of some mechanisms associated with osteoporosis. To determine some intrinsic mechanisms of the disease, therefore, animal models that mimic the postmenopausal osteoporosis are commonly used. In this study, we used ovariectomized female mice (OVX) as a model for postmenopausal osteoporosis, aiming to study phenomena associated with the bone tissue ultrastructure under conditions that can be of great importance for the treatment of the disease. For this purpose, were used a combination of histological and biochemical analyses as well as electronic microscopy, besides the gold standard in the diagnosis of osteoporosis: Dual X-ray Absorptiometry (DXA). The drop in circulating estrogen led to profound changes in different markers of bone formation and bone resorption, decreased BMD, and the presence of microfractures in bone tissue. From this characterization, were conducted two parallel studies, despite complementary, on the role of vitamin K - molecule believed to be essential for bone mineralization - and apolipoprotein E, a molecule that is also associated to increased risk of osteoporosis. Results obtained throughout this study demonstrated that supplementation with vitamin K in OVX animals led to profund changes in the ultrastructure of bone tissue (determined by analysis of scanning electronic microscopy). However, supplementation with vitamin K did not lead to such deep changes in biomarkers of the disease. In contrast, the loss of ApoE in genetically modified animals (APOEKO) significantly changed several serum biomarkers for the diagnosis of osteoporosis and the ultrastructure of tissue in OVX mice. Taken together, our results indicate - through a combination of ultrastructural analyses on bone tissue and measurement of biomarkers - that vitamin K affects mainly microfractures in OVX mice while the absence of the ApoE gene led to a decrease in BMD. Therefore, even if the axis estrogen-ApoE-vitamin K is well defined in the context of the pathogenesis of osteoporosis, our results pointed to different effects of these molecules on bone metabolism. |
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Rangel, Letícia Batista AzevedoSilva, Ian VictorSiqueira, Daniel deNogueira, Breno ValentimPacheco, Marcos da Silva2016-05-16T13:33:28Z2016-06-24T06:00:05Z2014-09-262014-09-26It is currently observed an increase in the incidence of osteometabolic diseases, particularly osteoporosis. This disease is caused by an imbalance between bone formation and bone resorption, closely linked to aging. In osteoporosis, it is observed that the predominance of bone resorption leads to a lower bone mineral density (BMD). It is believed that decrease in BMD is the main risk factor for bone breaking observed in these patients. Although low BMD represents the main risk factor for osteoporosis, this disease is multifactorial. Another remarkable feature in osteoporosis is its prevalence in postmenopausal women. It is now known that estrogen is one of the major factors responsible for the formation of bone tissue and its mineralization. Therefore, its deficiency at menopause results in a higher incidence of the disease in this population. Nevertheless studies in humans have contributed immensely to the understanding of the disease, the limitations imposed by the techniques to be used prevents the investigation of some mechanisms associated with osteoporosis. To determine some intrinsic mechanisms of the disease, therefore, animal models that mimic the postmenopausal osteoporosis are commonly used. In this study, we used ovariectomized female mice (OVX) as a model for postmenopausal osteoporosis, aiming to study phenomena associated with the bone tissue ultrastructure under conditions that can be of great importance for the treatment of the disease. For this purpose, were used a combination of histological and biochemical analyses as well as electronic microscopy, besides the gold standard in the diagnosis of osteoporosis: Dual X-ray Absorptiometry (DXA). The drop in circulating estrogen led to profound changes in different markers of bone formation and bone resorption, decreased BMD, and the presence of microfractures in bone tissue. From this characterization, were conducted two parallel studies, despite complementary, on the role of vitamin K - molecule believed to be essential for bone mineralization - and apolipoprotein E, a molecule that is also associated to increased risk of osteoporosis. Results obtained throughout this study demonstrated that supplementation with vitamin K in OVX animals led to profund changes in the ultrastructure of bone tissue (determined by analysis of scanning electronic microscopy). However, supplementation with vitamin K did not lead to such deep changes in biomarkers of the disease. In contrast, the loss of ApoE in genetically modified animals (APOEKO) significantly changed several serum biomarkers for the diagnosis of osteoporosis and the ultrastructure of tissue in OVX mice. Taken together, our results indicate - through a combination of ultrastructural analyses on bone tissue and measurement of biomarkers - that vitamin K affects mainly microfractures in OVX mice while the absence of the ApoE gene led to a decrease in BMD. Therefore, even if the axis estrogen-ApoE-vitamin K is well defined in the context of the pathogenesis of osteoporosis, our results pointed to different effects of these molecules on bone metabolism.Observa-se atualmente um aumento na incidência de doenças osteometabólicas, particularmente a osteoporose. Esta doença decorre de uma alteração do equilíbrio entre formação e reabsorção óssea, intimamente ligada ao avançar da idade. Na osteoporose, observa-se que o predomínio da reabsorção óssea acaba levando a redução da densidade mineral óssea (DMO). Acredita-se que a diminuição da DMO seja o principal fator de risco para a maior casuística de fraturas observada nestes pacientes. Ainda que a osteoporose apresente a queda na DMO como um fator de risco muito bem definido, esta doença é de caráter multifatorial. Outra característica marcante na osteoporose é sua prevalência em mulheres pós-menopausadas. Sabe-se hoje que o estrogênio é um dos principais fatores responsáveis pela formação de tecido ósseo e sua mineralização. Portanto, sua deficiência na menopausa resulta numa maior incidência da doença nesta população. Embora os estudos em seres humanos possam contribuir imensamente para o entendimento da doença, as limitações impostas pelas técnicas a serem utilizadas impede a investigação de alguns mecanismos associados à osteoporose. Para determinar alguns mecanismos intrínsecos a doença, portanto, são utilizados modelos animais que mimetizam a osteoporose pós-menopausa. Neste trabalho, utilizamos camundongos fêmeas ovariotectomizadas (OVX) como modelo para osteoporose pós-menopausa, visando estudar fenômenos associados à ultraestrutura do tecido ósseo em condições que podem ser de grande importância para o tratamento da doença. Para tanto foram utilizados uma combinação de análises histológicas, bioquímicas e microscopia eletrônica além do padrão ouro no diagnóstico de osteoporose: A Absorciometria dupla de raio-X (DXA). A queda do estrogênio circulante levou a profundas alterações em diferentes marcadores de reabsorção e formação óssea, queda da DMO e presença de microfraturas no tecido ósseo. Partindo desta caracterização, foram realizados dois estudos paralelos, porém complementares, sobre o papel da vitamina K – um agente que se acredita ser fundamental para mineralização óssea – e a apoliproteína E, molécula que se acredita estar associada também ao risco de osteoporose. Resultados obtidos ao longo deste trabalho demonstraram que a suplementação com vitamina K em animais OVX alterou a ultraestrutura do tecido ósseo (determinado por análises de microscopia eletrônica de varredura). Contudo, a suplementação com vitamina K não levou a alterações tão marcantes em biomarcadores da doença. Em contrapartida, a perda da ApoE em animais geneticamente modificados (APOEKO) alterou tanto os biomarcadores séricos utilizados no diagnóstico da osteoporose quanto a ultraestrutura do tecido em camundongos OVX. Tomados conjuntamente, nossos resultados indicam – através da combinação de análises ultraestruturais no tecido ósseo e mensuração de biomarcadores - que a vitamina K afeta majoritariamente as microfraturas em camundongos OVX enquanto que a ausência do gene ApoE levou à uma queda na DMO. Portanto, mesmo que o eixo estrogênio-ApoE-vitamina K seja bem definido no contexto da patogênese da osteoporose, nossos resultados apontaram para efeitos distintos destas moléculas no metabolismo ósseo.Texthttp://repositorio.ufes.br/handle/10/1880porUniversidade Federal do Espírito SantoDoutorado em BiotecnologiaPrograma de Pós-Graduação em BiotecnologiaUFESBRCentro de Ciências da SaúdeApolipoproteína EMicroscopia eletrônica de transmissãoOsteoporoseVitamina KMicroscopia eletrônica de varreduraBiotecnologia61Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizadosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESORIGINALTese Daniel de Siqueira.pdfTese Daniel de Siqueira.pdfapplication/pdf3819887http://repositorio.ufes.br/bitstreams/05ce0fb6-7a19-473d-87e6-31ef4a925353/download775c634df123886dc749019879e0e4a8MD51CC-LICENSElicense_urllicense_urltext/plain; charset=utf-849http://repositorio.ufes.br/bitstreams/6c00d024-396c-4daf-be5f-104463062b75/download4afdbb8c545fd630ea7db775da747b2fMD52license_textlicense_texttext/html; charset=utf-822064http://repositorio.ufes.br/bitstreams/f7bd0187-125f-430d-baf3-2d84d3fe613a/downloadef48816a10f2d45f2e2fee2f478e2fafMD53license_rdflicense_rdfapplication/rdf+xml; charset=utf-823148http://repositorio.ufes.br/bitstreams/638e2716-435e-4892-8241-b18ce3b70eb5/download9da0b6dfac957114c6a7714714b86306MD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufes.br/bitstreams/b6eac123-ec5f-433c-a8d8-e5f6f8d7c493/download8a4605be74aa9ea9d79846c1fba20a33MD5510/18802024-08-27 13:05:15.428oai:repositorio.ufes.br:10/1880http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-10-15T17:52:20.783678Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)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 |
dc.title.none.fl_str_mv |
Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados |
title |
Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados |
spellingShingle |
Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados Siqueira, Daniel de Apolipoproteína E Biotecnologia Microscopia eletrônica de transmissão Osteoporose Vitamina K Microscopia eletrônica de varredura 61 |
title_short |
Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados |
title_full |
Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados |
title_fullStr |
Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados |
title_full_unstemmed |
Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados |
title_sort |
Osteoporose : uma análise ultraestrutural do tecido ósseo em camundongos C57 e apoeko ovariotectomizados |
author |
Siqueira, Daniel de |
author_facet |
Siqueira, Daniel de |
author_role |
author |
dc.contributor.advisor-co1.fl_str_mv |
Rangel, Letícia Batista Azevedo |
dc.contributor.advisor1.fl_str_mv |
Silva, Ian Victor |
dc.contributor.author.fl_str_mv |
Siqueira, Daniel de |
dc.contributor.referee1.fl_str_mv |
Nogueira, Breno Valentim |
dc.contributor.referee2.fl_str_mv |
Pacheco, Marcos da Silva |
contributor_str_mv |
Rangel, Letícia Batista Azevedo Silva, Ian Victor Nogueira, Breno Valentim Pacheco, Marcos da Silva |
dc.subject.por.fl_str_mv |
Apolipoproteína E |
topic |
Apolipoproteína E Biotecnologia Microscopia eletrônica de transmissão Osteoporose Vitamina K Microscopia eletrônica de varredura 61 |
dc.subject.cnpq.fl_str_mv |
Biotecnologia |
dc.subject.br-rjbn.none.fl_str_mv |
Microscopia eletrônica de transmissão Osteoporose Vitamina K Microscopia eletrônica de varredura |
dc.subject.udc.none.fl_str_mv |
61 |
description |
It is currently observed an increase in the incidence of osteometabolic diseases, particularly osteoporosis. This disease is caused by an imbalance between bone formation and bone resorption, closely linked to aging. In osteoporosis, it is observed that the predominance of bone resorption leads to a lower bone mineral density (BMD). It is believed that decrease in BMD is the main risk factor for bone breaking observed in these patients. Although low BMD represents the main risk factor for osteoporosis, this disease is multifactorial. Another remarkable feature in osteoporosis is its prevalence in postmenopausal women. It is now known that estrogen is one of the major factors responsible for the formation of bone tissue and its mineralization. Therefore, its deficiency at menopause results in a higher incidence of the disease in this population. Nevertheless studies in humans have contributed immensely to the understanding of the disease, the limitations imposed by the techniques to be used prevents the investigation of some mechanisms associated with osteoporosis. To determine some intrinsic mechanisms of the disease, therefore, animal models that mimic the postmenopausal osteoporosis are commonly used. In this study, we used ovariectomized female mice (OVX) as a model for postmenopausal osteoporosis, aiming to study phenomena associated with the bone tissue ultrastructure under conditions that can be of great importance for the treatment of the disease. For this purpose, were used a combination of histological and biochemical analyses as well as electronic microscopy, besides the gold standard in the diagnosis of osteoporosis: Dual X-ray Absorptiometry (DXA). The drop in circulating estrogen led to profound changes in different markers of bone formation and bone resorption, decreased BMD, and the presence of microfractures in bone tissue. From this characterization, were conducted two parallel studies, despite complementary, on the role of vitamin K - molecule believed to be essential for bone mineralization - and apolipoprotein E, a molecule that is also associated to increased risk of osteoporosis. Results obtained throughout this study demonstrated that supplementation with vitamin K in OVX animals led to profund changes in the ultrastructure of bone tissue (determined by analysis of scanning electronic microscopy). However, supplementation with vitamin K did not lead to such deep changes in biomarkers of the disease. In contrast, the loss of ApoE in genetically modified animals (APOEKO) significantly changed several serum biomarkers for the diagnosis of osteoporosis and the ultrastructure of tissue in OVX mice. Taken together, our results indicate - through a combination of ultrastructural analyses on bone tissue and measurement of biomarkers - that vitamin K affects mainly microfractures in OVX mice while the absence of the ApoE gene led to a decrease in BMD. Therefore, even if the axis estrogen-ApoE-vitamin K is well defined in the context of the pathogenesis of osteoporosis, our results pointed to different effects of these molecules on bone metabolism. |
publishDate |
2014 |
dc.date.submitted.none.fl_str_mv |
2014-09-26 |
dc.date.issued.fl_str_mv |
2014-09-26 |
dc.date.accessioned.fl_str_mv |
2016-05-16T13:33:28Z |
dc.date.available.fl_str_mv |
2016-06-24T06:00:05Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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http://repositorio.ufes.br/handle/10/1880 |
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http://repositorio.ufes.br/handle/10/1880 |
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por |
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openAccess |
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Text |
dc.publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Doutorado em Biotecnologia |
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Programa de Pós-Graduação em Biotecnologia |
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UFES |
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BR |
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Centro de Ciências da Saúde |
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Universidade Federal do Espírito Santo Doutorado em Biotecnologia |
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