Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | http://tede2.pucrs.br/tede2/handle/tede/8172 |
Resumo: | This thesis encompasses two parts: firstly, we compared the bone healing in female and male mice, after induction of type 1 diabetes (T1D); secondly, the bone regeneration was evaluated in a menopause model induced by bilateral ovariectomy (OVX), with or without T1D induction. For the part I, the animals (female and male) were initially assigned into two groups, namely control or T1D (elicited by streptozotocin; STZ). In the part II, the females were divided into four experimental groups: sham-operated or OVX, with or without STZ T1D induction. After T1D induction, a monocortical femoral defect was created. In either parts of the present study, we evaluated the effects of supplementation with vitamin D3 and/or insulin. In the second part, the effects of estrogen replacement were also analyzed. Following 21 days of bone defect creation, the animals were euthanized; the femurs and blood were collected for posterior analysis. Both T1D females and males presented a reduction in body weight gain, associated with hyperglycemia. There were no changes in the serum levels of the pro-inflammatory cytokines [interleukin-1 (IL-1), tumor necrosis factor (TNF) and interferon- (IFN-)] in all the evaluated groups. T1D mice of both sexes presented a delayed bone regeneration, according to the histological and micro-CT assessment. The supplementation with vitamin D3 restored the bone healing in female and male T1D mice, reaching values close to controls. The insulin therapy improved the bone remodeling in T1D mice of both sexes, but the effects of this hormone were superior in males. The evaluation of osteoclast activity did not reveal significant differences among the experimental groups. Real time PCR revealed slight differences in the mRNA expression of two transcription factors related to osteoblast differentiation, namely runx2 and osterix, as measured in the area into the bone defect. A higher upregulation of both factors was seen in T1D males treated with vitamin D3. Conversely, vitamin D3-treated T1D females displayed an upregulation of insulin-like growth factor 1 (IGF-1), further indication sex-related differences for the treatments. Besides the experimental protocols described for the 12 part I of this thesis, in the part II, we also evaluated some behavioral locomotor parameters and serum levels of calcium and alkaline phosphatase. OVX animals presented increased body weight gain, accompanied by uterus atrophy. Otherwise, T1D induction elicited a reduction of body weight gain, which was more pronounced in OVX-T1D animals. Serum levels of alkaline phosphatase were divergent in the non-diabetic and T1D OVX animals. Calcium or cytokine levels were similar in all the experimental groups. The sham-operated T1D, the non-diabetic OVX and the OVX-T1D groups presented a delayed bone regeneration, as indicated by histological and micro-CT analysis. Estrogen replacement improved the bone healing in all OVX groups. There was a trend toward an upregulation of IGF-1 mRNA in non-diabetic OVX animals, which was not mirrored in OVX-T1D mice. Locomotor parameters remained unaltered, except by a general reduction of rearing numbers in T1D animals. |
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Campos, Maria Marthahttp://lattes.cnpq.br/3601505933558375http://lattes.cnpq.br/8360274710097789Cignachi, Natália Pradella2018-06-27T14:43:00Z2018-01-25http://tede2.pucrs.br/tede2/handle/tede/8172This thesis encompasses two parts: firstly, we compared the bone healing in female and male mice, after induction of type 1 diabetes (T1D); secondly, the bone regeneration was evaluated in a menopause model induced by bilateral ovariectomy (OVX), with or without T1D induction. For the part I, the animals (female and male) were initially assigned into two groups, namely control or T1D (elicited by streptozotocin; STZ). In the part II, the females were divided into four experimental groups: sham-operated or OVX, with or without STZ T1D induction. After T1D induction, a monocortical femoral defect was created. In either parts of the present study, we evaluated the effects of supplementation with vitamin D3 and/or insulin. In the second part, the effects of estrogen replacement were also analyzed. Following 21 days of bone defect creation, the animals were euthanized; the femurs and blood were collected for posterior analysis. Both T1D females and males presented a reduction in body weight gain, associated with hyperglycemia. There were no changes in the serum levels of the pro-inflammatory cytokines [interleukin-1 (IL-1), tumor necrosis factor (TNF) and interferon- (IFN-)] in all the evaluated groups. T1D mice of both sexes presented a delayed bone regeneration, according to the histological and micro-CT assessment. The supplementation with vitamin D3 restored the bone healing in female and male T1D mice, reaching values close to controls. The insulin therapy improved the bone remodeling in T1D mice of both sexes, but the effects of this hormone were superior in males. The evaluation of osteoclast activity did not reveal significant differences among the experimental groups. Real time PCR revealed slight differences in the mRNA expression of two transcription factors related to osteoblast differentiation, namely runx2 and osterix, as measured in the area into the bone defect. A higher upregulation of both factors was seen in T1D males treated with vitamin D3. Conversely, vitamin D3-treated T1D females displayed an upregulation of insulin-like growth factor 1 (IGF-1), further indication sex-related differences for the treatments. Besides the experimental protocols described for the 12 part I of this thesis, in the part II, we also evaluated some behavioral locomotor parameters and serum levels of calcium and alkaline phosphatase. OVX animals presented increased body weight gain, accompanied by uterus atrophy. Otherwise, T1D induction elicited a reduction of body weight gain, which was more pronounced in OVX-T1D animals. Serum levels of alkaline phosphatase were divergent in the non-diabetic and T1D OVX animals. Calcium or cytokine levels were similar in all the experimental groups. The sham-operated T1D, the non-diabetic OVX and the OVX-T1D groups presented a delayed bone regeneration, as indicated by histological and micro-CT analysis. Estrogen replacement improved the bone healing in all OVX groups. There was a trend toward an upregulation of IGF-1 mRNA in non-diabetic OVX animals, which was not mirrored in OVX-T1D mice. Locomotor parameters remained unaltered, except by a general reduction of rearing numbers in T1D animals.A presente tese está dividida em duas partes: na parte I, comparou-se a regeneração óssea em camundongos fêmeas e machos, com diabetes do tipo 1 (T1D). Na parte II, foi avaliada a regeneração óssea no modelo de menopausa experimental induzido por ovariectomia (OVX), com ou sem T1D. Na parte I, os animais (machos e fêmeas) foram divididos em dois grandes grupos: controle e T1D (induzido por estreptozotocina; STZ). Na parte II, os animais foram divididos em quatro grandes grupos: fêmeas falso-operadas e OVX, com ou sem T1D. Após a indução do T1D, foi criado um defeito ósseo monocortical no fêmur. Nas duas partes do trabalho, foram avaliados os efeitos da suplementação com vitamina D3 e/ou insulina. Na segunda parte, também se avaliou o efeito da reposição hormonal com estradiol. Decorridos 21 dias do procedimento da criação do defeito, os animais foram eutanasiados; o fêmur e o sangue foram coletados para análises posteriores. Tanto as fêmeas, quanto os machos T1D, apresentaram uma redução do ganho de peso corporal, associado à hiperglicemia. Não houve alterações nos níveis séricos das citocinas pró-inflamatórias interleucina-1 (IL-1), fator de necrose tumoral (TNF) ou interferon- (IFN). Os animais T1D, de ambos os sexos, apresentaram um comprometimento na regeneração óssea, como demonstrado pelas análises histológicas e de micro-CT. A suplementação com vitamina D3 reestabeleceu a regeneração óssea em fêmeas e machos T1D, apresentando valores próximos aos encontrados nos animais do grupo controle. A terapia com insulina melhorou a remodelação óssea nas fêmeas e machos T1D; porém, os efeitos foram mais pronunciados nos machos. A avaliação da atividade osteoclástica não revelou diferenças significativas entre os grupos experimentais, após a indução de T1D, em machos ou fêmeas. Os resultados do PCR em tempo real para runx2 e osterix (dois fatores de transcrição relacionados aos osteoblastos), no tecido ósseo, não demonstraram nenhuma diferença significativa, exceto por um aumento nos níveis de RNAm dos dois fatores nos camundongos machos T1D, que receberam suplementação com vitamina 10 D3. Por outro lado, fêmeas T1D que receberam vitamina D3 apresentaram um aumento na expressão dos níveis de RNAm para o fator de crescimento semelhante à insulina do tipo 1 (IGF-1), quando comparado com os machos que tiveram o mesmo tratamento, sugerindo assim, diferenças relacionadas ao sexo. Além das análises já mencionadas anteriormente, na parte II da tese, parâmetros comportamentais e níveis séricos de cálcio e fosfatase alcalina também foram analisados. Os resultados da segunda parte do trabalho demonstraram que os animais submetidos a OVX tiveram um aumento do peso corporal, com atrofia uterina. Em contrapartida, quando foi induzido T1D, houve uma diminuição do peso corporal mais acentuada no grupo OVX que no grupo falso-operado. Os animais falso-operados e OVX T1D apresentaram hiperglicemia, confirmando o desenvolvimento do diabetes. Os níveis séricos de fosfatase alcalina foram divergentes entre os grupos não-diabéticos OVX e OVX T1D. Não houve variações dos níveis de cálcio. Os animais falso-operados T1D, não diabéticos OVX e OVX T1D apresentaram prejuízos similares na regeneração óssea, como observado pelas análises histológicas e imagens de micro-CT. A reposição com estradiol melhorou a cicatrização óssea nos animais não-diabéticos OVX e OVX T1D. Houve uma tendência ao aumento nos níveis de RNAm de IGF-1 no grupo OVX, o que não foi observado quando da associação de T1D e menopausa. Não foram observadas diferenças na atividade locomotora dos animais com T1D e/ou OVX, a não ser por uma diminuição no número de rearings no grupo falso-operado T1D, independente do tratamento com vitamina D3, insulina e estradiol, de forma isolada ou em associação.Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2018-06-04T18:05:30Z No. of bitstreams: 1 NATALIA_PRADELLA_CIGNACHI_TES.pdf: 6840858 bytes, checksum: 8e5f3ae6a98395bf09135b6770903f35 (MD5)Rejected by Sheila Dias (sheila.dias@pucrs.br), reason: Devolvido devido à falta da capa institucional no arquivo em PDF. on 2018-06-14T14:34:13Z (GMT)Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2018-06-19T13:28:41Z No. of bitstreams: 1 NATÁLIA_PREDELLA_CIGNACHI_TES.pdf: 11102267 bytes, checksum: 121fbf4d2b9ae1c4a36e21d23ab3140d (MD5)Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-06-27T14:32:32Z (GMT) No. of bitstreams: 1 NATÁLIA_PREDELLA_CIGNACHI_TES.pdf: 11102267 bytes, checksum: 121fbf4d2b9ae1c4a36e21d23ab3140d (MD5)Made available in DSpace on 2018-06-27T14:43:00Z (GMT). No. of bitstreams: 1 NATÁLIA_PREDELLA_CIGNACHI_TES.pdf: 11102267 bytes, checksum: 121fbf4d2b9ae1c4a36e21d23ab3140d (MD5) Previous issue date: 2018-01-25Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/172654/TES_NATALIA_PREDELLA_CIGNACHI_CONFIDENCIAL.pdf.jpghttp://tede2.pucrs.br:80/tede2/retrieve/179011/TES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em OdontologiaPUCRSBrasilEscola de Ciências da SaúdeRegeneração ÓsseaDiabetes Tipo 1Camundongos Machos e FêmeasInsulinaVitamina D3EstrogênioOvariectomiaMenopausaBone RegenerationType 1 DiabetesMalesFemalesInsulinVitamin D3OvariectomyMenopauseCIENCIAS DA SAUDE::ODONTOLOGIARegeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimentalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTrabalho será publicado como artigo ou livro24 meses27/06/2020-8096554818733665164500500600-20704984698792443492075167498588264571info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSORIGINALTES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdfTES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdfapplication/pdf11102267http://tede2.pucrs.br/tede2/bitstream/tede/8172/7/TES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdf121fbf4d2b9ae1c4a36e21d23ab3140dMD57THUMBNAILTES_NATALIA_PREDELLA_CIGNACHI_CONFIDENCIAL.pdf.jpgTES_NATALIA_PREDELLA_CIGNACHI_CONFIDENCIAL.pdf.jpgimage/jpeg4090http://tede2.pucrs.br/tede2/bitstream/tede/8172/6/TES_NATALIA_PREDELLA_CIGNACHI_CONFIDENCIAL.pdf.jpge8d1dfbcf8429c47d93f016fb76d1410MD56TES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdf.jpgTES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdf.jpgimage/jpeg4488http://tede2.pucrs.br/tede2/bitstream/tede/8172/9/TES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdf.jpg165301f3ee849352ad3ffba2bdf0a926MD59TEXTTES_NATALIA_PREDELLA_CIGNACHI_CONFIDENCIAL.pdf.txtTES_NATALIA_PREDELLA_CIGNACHI_CONFIDENCIAL.pdf.txttext/plain2092http://tede2.pucrs.br/tede2/bitstream/tede/8172/5/TES_NATALIA_PREDELLA_CIGNACHI_CONFIDENCIAL.pdf.txt71d20127c33712c609a9dae9a38b1ad1MD55TES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdf.txtTES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdf.txttext/plain166536http://tede2.pucrs.br/tede2/bitstream/tede/8172/8/TES_NATALIA_PRADELLA_CIGNACHI_COMPLETO.pdf.txt4c3b1de0ca2907a19264b6ca7b4ad464MD58LICENSElicense.txtlicense.txttext/plain; charset=utf-8610http://tede2.pucrs.br/tede2/bitstream/tede/8172/3/license.txt5a9d6006225b368ef605ba16b4f6d1beMD53tede/81722020-10-19 13:00:23.895oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2020-10-19T15:00:23Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental |
title |
Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental |
spellingShingle |
Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental Cignachi, Natália Pradella Regeneração Óssea Diabetes Tipo 1 Camundongos Machos e Fêmeas Insulina Vitamina D3 Estrogênio Ovariectomia Menopausa Bone Regeneration Type 1 Diabetes Males Females Insulin Vitamin D3 Ovariectomy Menopause CIENCIAS DA SAUDE::ODONTOLOGIA |
title_short |
Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental |
title_full |
Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental |
title_fullStr |
Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental |
title_full_unstemmed |
Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental |
title_sort |
Regeneração óssea em camundongos : correlação entre diabetes tipo 1 e menopausa experimental |
author |
Cignachi, Natália Pradella |
author_facet |
Cignachi, Natália Pradella |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Campos, Maria Martha |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3601505933558375 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8360274710097789 |
dc.contributor.author.fl_str_mv |
Cignachi, Natália Pradella |
contributor_str_mv |
Campos, Maria Martha |
dc.subject.por.fl_str_mv |
Regeneração Óssea Diabetes Tipo 1 Camundongos Machos e Fêmeas Insulina Vitamina D3 Estrogênio Ovariectomia Menopausa |
topic |
Regeneração Óssea Diabetes Tipo 1 Camundongos Machos e Fêmeas Insulina Vitamina D3 Estrogênio Ovariectomia Menopausa Bone Regeneration Type 1 Diabetes Males Females Insulin Vitamin D3 Ovariectomy Menopause CIENCIAS DA SAUDE::ODONTOLOGIA |
dc.subject.eng.fl_str_mv |
Bone Regeneration Type 1 Diabetes Males Females Insulin Vitamin D3 Ovariectomy Menopause |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::ODONTOLOGIA |
description |
This thesis encompasses two parts: firstly, we compared the bone healing in female and male mice, after induction of type 1 diabetes (T1D); secondly, the bone regeneration was evaluated in a menopause model induced by bilateral ovariectomy (OVX), with or without T1D induction. For the part I, the animals (female and male) were initially assigned into two groups, namely control or T1D (elicited by streptozotocin; STZ). In the part II, the females were divided into four experimental groups: sham-operated or OVX, with or without STZ T1D induction. After T1D induction, a monocortical femoral defect was created. In either parts of the present study, we evaluated the effects of supplementation with vitamin D3 and/or insulin. In the second part, the effects of estrogen replacement were also analyzed. Following 21 days of bone defect creation, the animals were euthanized; the femurs and blood were collected for posterior analysis. Both T1D females and males presented a reduction in body weight gain, associated with hyperglycemia. There were no changes in the serum levels of the pro-inflammatory cytokines [interleukin-1 (IL-1), tumor necrosis factor (TNF) and interferon- (IFN-)] in all the evaluated groups. T1D mice of both sexes presented a delayed bone regeneration, according to the histological and micro-CT assessment. The supplementation with vitamin D3 restored the bone healing in female and male T1D mice, reaching values close to controls. The insulin therapy improved the bone remodeling in T1D mice of both sexes, but the effects of this hormone were superior in males. The evaluation of osteoclast activity did not reveal significant differences among the experimental groups. Real time PCR revealed slight differences in the mRNA expression of two transcription factors related to osteoblast differentiation, namely runx2 and osterix, as measured in the area into the bone defect. A higher upregulation of both factors was seen in T1D males treated with vitamin D3. Conversely, vitamin D3-treated T1D females displayed an upregulation of insulin-like growth factor 1 (IGF-1), further indication sex-related differences for the treatments. Besides the experimental protocols described for the 12 part I of this thesis, in the part II, we also evaluated some behavioral locomotor parameters and serum levels of calcium and alkaline phosphatase. OVX animals presented increased body weight gain, accompanied by uterus atrophy. Otherwise, T1D induction elicited a reduction of body weight gain, which was more pronounced in OVX-T1D animals. Serum levels of alkaline phosphatase were divergent in the non-diabetic and T1D OVX animals. Calcium or cytokine levels were similar in all the experimental groups. The sham-operated T1D, the non-diabetic OVX and the OVX-T1D groups presented a delayed bone regeneration, as indicated by histological and micro-CT analysis. Estrogen replacement improved the bone healing in all OVX groups. There was a trend toward an upregulation of IGF-1 mRNA in non-diabetic OVX animals, which was not mirrored in OVX-T1D mice. Locomotor parameters remained unaltered, except by a general reduction of rearing numbers in T1D animals. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-06-27T14:43:00Z |
dc.date.issued.fl_str_mv |
2018-01-25 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
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http://tede2.pucrs.br/tede2/handle/tede/8172 |
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http://tede2.pucrs.br/tede2/handle/tede/8172 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
-8096554818733665164 |
dc.relation.confidence.fl_str_mv |
500 500 600 |
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-2070498469879244349 |
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2075167498588264571 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Pontifícia Universidade Católica do Rio Grande do Sul |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Odontologia |
dc.publisher.initials.fl_str_mv |
PUCRS |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Escola de Ciências da Saúde |
publisher.none.fl_str_mv |
Pontifícia Universidade Católica do Rio Grande do Sul |
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