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Effect of thyroid hormone and its antagonist NH3 in osteoblastic differentiation of human periosteal mesenchymal cells with mutation in FGFR2 that cause Apert Syndrome.

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Author(s):
Cristiane Cabral Costa
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Cecilia Helena de Azevedo Gouveia Ferreira; Maria Rita dos Santos e Passos Bueno; Marise Lazaretti Castro; Victor Elias Arana Chavez; Rosa Maria Rodrigues Pereira
Advisor: Cecilia Helena de Azevedo Gouveia Ferreira; Maria Rita dos Santos e Passos Bueno
Abstract

Evidence suggests that there is an interaction between the thyroid hormone (T3) and fibroblast growth factors (FGFs) in the skeletal development. To study this interaction, we evaluated the effect of T3 and its antagonist, NH3, in human periosteal mesenchymal cells from normal and Apert Syndrome (AS) patients, which is characterized by craniosynostosis and is caused by mutations in FGF receptor type 2 (FGFR2). In AS cells, the T3 increased the number of cells and NH3 blocked this effect of T3. T3 and/or NH3 increased the alkaline phosphatase activity in osteoblast differentiation of normal cells, but not in the mutated cells. T3 increased osteoblast differentiation and NH3 blocked this effect of T3 on normal cells. In the mutated cells, NH3 limited osteoblast differentiation while T3 had no effect. We concluded that normal and AS human periosteal mesenchymal cells are responsive to T3 and NH3, and T3 and FGF may act through common signaling pathways in the regulation of osteoblastic differentiation. (AU)