The Thyroid Hormone Receptor (TR) beta-Selective Agonist GC-1 Inhibits Proliferation But Induces Differentiation and TR beta mRNA Expression in Mouse and Rat Osteoblast-Like Cells

Autor(es)

Beber, Eduardo H. ^[1] ; Capelo, Luciane P. ^[2] ; Fonseca, Tatiana L. ^[1] ; Costa, Cristiane C. ^[1] ; Lotfi, Claudimara F. ^[1] ; Scanlan, Thomas S. ^[3] ; Gouveia, Cecilia H. A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508000 Sao Paulo - Brazil

^[3] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 - USA

• Tipo de documento: Artigo Científico
• Fonte: CALCIFIED TISSUE INTERNATIONAL; v. 84, n. 4, p. 324-333, APR 2009.
• Citações Web of Science: 14

Resumo

Previous studies showed anabolic effects of GC-1, a triiodothyronine (T3) analogue that is selective for both binding and activation functions of thyroid hormone receptor (TR) beta 1 over TR alpha 1, on bone tissue in vivo. The aim of this study was to investigate the responsiveness of rat (ROS17/2.8) and mouse (MC3T3-E1) osteoblast-like cells to GC-1. As expected, T3 inhibited cellular proliferation and stimulated mRNA expression of osteocalcin or alkaline phosphatase in both cell lineages. Whereas equimolar doses of T3 and GC-1 equally affected these parameters in ROS17/2.8 cells, the effects of GC-1 were more modest compared to those of T3 in MC3T3-E1 cells. Interestingly, we showed that there is higher expression of TR alpha 1 than TR beta 1 mRNA in rat (similar to 20-90%) and mouse (similar to 90-98%) cell lineages and that this difference is even higher in mouse cells, which highlights the importance of TR alpha 1 to bone physiology and may partially explain the modest effects of GC-1 in comparison with T3 in MC3T3-E1 cells. Nevertheless, we showed that TR beta 1 mRNA expression increases (similar to 2.8- to 4.3-fold) as osteoblastic cells undergo maturation, suggesting a key role of TR beta 1 in mediating T3 effects in the bone forming cells, especially in mature osteoblasts. It is noteworthy that T3 and GC-1 induced TR beta 1 mRNA expression to a similar extent in both cell lineages (similar to 2- to 4-fold), indicating that both ligands may modulate the responsiveness of osteoblasts to T3. Taken together, these data show that TR beta selective T3 analogues have the potential to directly induce the differentiation and activity of osteoblasts. (AU)

• Processo FAPESP: 05/52910-4 - Efeito da reposição de hormônio do crescimento no desenvolvimento ósseo de ratas hipotiroideas tratadas com o tiromimético seletivo do receptor beta do hormônio tiroideano GC-1
• Beneficiário: Cecilia Helena de Azevedo Gouveia
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/52982-8 - Efeito do hormônio tiroideano e do seu análogo seletivo pelo TRbeta, o CG-1, sobre parâmetros histomorfométricos do tecido ósseo de ratas Wistar adultas
• Beneficiário: Cristiane Cabral Costa
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 05/59557-8 - Estudo da interação do hormônio tiroideano com o sistema nervoso simpático na regulação da massa e metabolismo ósseos
• Beneficiário: Tatiana de Lourdes Fonseca
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 03/07327-3 - Expressão gênica das selenodesiodases das iodotironinas no esqueleto de camundongos durante o desenvolvimento pré-natal
• Beneficiário: Luciane Portas Capelo
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto