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Regulation Of Igfbp-5 And Osteoblast Functions By Nuclear Factor I, Laura A. Perez-Casellas
Regulation Of Igfbp-5 And Osteoblast Functions By Nuclear Factor I, Laura A. Perez-Casellas
Loma Linda University Electronic Theses, Dissertations & Projects
The Insulin-like Growth Factor (IGF) system is a major target of GC inhibition in bone. We found that GCs inhibit expression of IGF binding protein-5 (IGFBP5) which binds IGFs and stimulates osteoblast activity by IGF dependent and independent mechanisms. GC-induced inhibition of IGFPB5 promoter activity was mediated by a composite response element that has binding sites for transcription factor activator protein 2 (AP-2) and nuclear factor I (NFI). The work in this dissertation identifies the NFI gene family as an important regulator of IGFBP-5 transcription primarily in human, as well as murine osteoblasts. The mechanism of IGFBP5 gene regulation involves …