Efeito da triiodotironina (T3) e estrógeno (E2) Sobre a expressão gênica e proteica de Rankl, OPG E c-Fos em osteoblastos derivados de células tronco mesenquimais humanas
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Data
2017-02-23
Autores
Olímpio, Regiane Marques Castro [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
O tecido ósseo é extremamente complexo e regulado por fatores sistêmicos e locais, apresentando considerável atividade metabólica que envolve a remoção do osso mineralizado pelos osteoclastos, seguida pela formação da matriz óssea pelos osteoblastos. A associação de triiodotironina (T3) e estrógeno (E2) pode levar a uma resposta complexa à atividade do tecido ósseo sendo que o T3 possui efeito tanto sobre a reabsorção como na formação óssea e o E2, em baixo nível, pode levar a osteoporose e no estado normal garante a supressão de citocinas, a partir do sistema RANKL, OPG e c-Fos, que participam ativamente no remodelamento ósseo. Dessa forma, muitos estudos têm sido realizados com o objetivo de verificar a ação hormonal sobre o metabolismo ósseo. Entre essas pesquisas, têm sido isoladas células-tronco mesenquimais (CTMs) a partir do tecido adiposo humano e diferenciadas em osteoblastos. Baseado nisso, o objetivo do nosso trabalho foi avaliar o efeito do T3 e E2 nas concentrações infrafisiológica (T3I/ 10-10M e E2I/ 10-9M); fisiológicas (T3F/10-9M e E2F/10-8M) e suprafisiológicas (T3S/10-8M) separadamente e em diferentes associações de T3I (T3I+E2I e T3I+E2F); T3F (T3F+E2I e T3F+E2F) e T3S (T3S+E2I e T3S + E2F) e diferentes associações de E2I (E2I+T3I e E2I+T3F e E2I+T3S); E2F (E2F+T3I e E2F+T3F e E2F+T3S) sobre a expressão gênica e proteica de RANKL, OPG e c-FOS. Quando associados, a maioria desses hormônios aumentou os níveis gênicos da célula estudada. Em conclusão, podemos afirmar que as doses analisadas de T3 e E2, foram capazes de aumentar os níveis gênicos e a síntese proteica de RANKL, OPG e c-FOS e que principalmente nas associações foi eficaz para aumentar a expressão gênica desses genes.
Bone tissue is extremely complex and is regulated by systemic and local factors, presenting a considerable metabolic activity involving the removal of mineralized bone by osteoclasts in balance with the formation of bone matrix by osteoblasts. The association of triiodothyronine (T3) and estrogen (E2) may lead the activity of bone tissue to complex responses, due to T3 effects on both bone formation and reabsorption, and E2 being able to lead to osteoporosis when at low levels, or, at normal levels, maintain the suppression of the cytokines RANKL, OPG, and c-FOS, which take part actively on bone remodeling. To date, many studies have been done to verify hormone actions on bone metabolism. Among them, mesenchymal stem cells (MSC) have been isolated from human adipose tissue and differentiated into osteoblasts. The aim of our study was to evaluate the effect of both T3 and E2 on RANKL, OPG, and c-FOS gene and protein expression, at infra- (T3I, 10-10M; E2I, 10-9M), physiological (T3F, 10-9M; E2F, 10-8M) supra- (T3S, 10-8M) and doses. Cells were treated with hormones separately or in all possible combinations of T3 and E2 doses. The majority of associated treatments increased gene expression levels of all genes. We can state that the doses included in this study, of both hormones, efficiently increase the expression of the analyzed genes, especially when associated.
Bone tissue is extremely complex and is regulated by systemic and local factors, presenting a considerable metabolic activity involving the removal of mineralized bone by osteoclasts in balance with the formation of bone matrix by osteoblasts. The association of triiodothyronine (T3) and estrogen (E2) may lead the activity of bone tissue to complex responses, due to T3 effects on both bone formation and reabsorption, and E2 being able to lead to osteoporosis when at low levels, or, at normal levels, maintain the suppression of the cytokines RANKL, OPG, and c-FOS, which take part actively on bone remodeling. To date, many studies have been done to verify hormone actions on bone metabolism. Among them, mesenchymal stem cells (MSC) have been isolated from human adipose tissue and differentiated into osteoblasts. The aim of our study was to evaluate the effect of both T3 and E2 on RANKL, OPG, and c-FOS gene and protein expression, at infra- (T3I, 10-10M; E2I, 10-9M), physiological (T3F, 10-9M; E2F, 10-8M) supra- (T3S, 10-8M) and doses. Cells were treated with hormones separately or in all possible combinations of T3 and E2 doses. The majority of associated treatments increased gene expression levels of all genes. We can state that the doses included in this study, of both hormones, efficiently increase the expression of the analyzed genes, especially when associated.
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Palavras-chave
Células-tronco mesenquimais, Triiodotironina, Estrógeno, Osteoblasto, Mesenchymal stem cells, Triiodothyronine, Estrogen, RANKL, OPG, cFOS, Osteoblast