TIEG1 enhances Osterix expression and mediates its induction by TGFβ and BMP2 in osteoblasts

Biochemical and Biophysical Research Communications
M SubramaniamJ R Hawse

Abstract

Deletion of TIEG1/KLF10 in mice results in an osteopenic skeletal phenotype with significant decreases in both bone mineral density and content throughout the skeleton. Calvarial osteoblasts isolated from TIEG1 knockout (KO) mice display numerous changes in gene expression and exhibit significant delays in their mineralization rates relative to wild-type (WT) controls. Here, we demonstrate that loss of TIEG1 expression in osteoblasts results in decreased levels of Osterix mRNA. Suppression of TIEG1 expression in WT osteoblasts leads to decreased Osterix expression while restoration of TIEG1 expression in TIEG1 KO osteoblasts results in increased levels of Osterix. Transient transfection and chromatin immunoprecipitation assays reveal that TIEG1 directly binds to and activates the Osterix promoter and demonstrate that the zinc finger-containing DNA binding domain of TIEG1 is necessary for this regulation. Furthermore, we reveal that TIEG1 expression is essential for the induction of Osterix expression by important bone-related cytokines such as TGFβ and BMP2 in osteoblast cells. Taken together, these data implicate an important role for TIEG1 in regulating the expression of Osterix, a master regulator of osteoblast differentiati...Continue Reading

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Citations

Dec 4, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Heeseog KangJoan C Marini
Feb 16, 2017·Nucleic Acids Research·Malayannan SubramaniamJohn R Hawse
Oct 19, 2017·Journal of Cellular Physiology·Malayannan SubramaniamJohn R Hawse
Sep 29, 2019·Acta Physiologica·Malek KammounSabine F Bensamoun
Mar 8, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jong Min LeeGun-Il Im
Oct 28, 2020·Cancer Immunology, Immunotherapy : CII·Ruishi ZhangGuohui Nie
Jan 2, 2021·Frontiers in Cell and Developmental Biology·Qian LiuGuangwei Wang

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