Parathyroid Hormone Regulates Osterix Promoter Activity In Vitro and Expression In Vivo

• Main Author: Barbuto, Richard
• Other Authors: Mitchell, Jane A.
• Language: en_ca
• Published: 2011
• Subjects: Osterix; osteoblast; parathyroid hormone; gene regulation; 0419
• Online Access: http://hdl.handle.net/1807/30175

Osterix (Osx) is a transcription factor required for osteoblast differentiation and bone formation. We previously demonstrated that continuous parathyroid hormone (PTH) treatment inhibited Osx expression in murine calvaria and osteoblastic UMR106-01 cells through the regulation of two regions on the Osx promoter. Mutational analysis of transcription factor elements within these regions revealed two "Sp-sites" were vital for Osx promoter activity. Blockage of these Sp-sites with Mithramycin A demonstrated their importance for Osx expression. Osx bound to its own promoter at these sites, while PTH treatment inhibited this association. PTH regulation of Osx expression in vivo was investigated in mice by: daily injection of PTH for 3 days, continuous infusion of PTH from osmotic pumps for 14 days, or mice fed a calcium-deficient diet for 21 days. Osx expression was decreased by daily injection, while Osx expression was stimulated in mice receiving continuous PTH infusion and mice fed a calcium-deficient diet.