GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2 |
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| Authors: | Insun Song Kabsun Kim Jung Ha Kim Young-Kyoung Lee Hyun-Jung Jung Hae-Ok Byun Gyesoon Yoon Nacksung Kim |
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| Institution: | 1.Department of Biochemistry, Ajou University School of Medicine & Chonnam National University Medical School, Gwangju 501-746, Korea;2.Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 443-721, Korea;3.Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-746, Korea;4.Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, Korea |
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| Abstract: | Osteoblasts are specialized mesenchymal cells that are responsible for bone formation. In this study, we examine the role of GATA4 in osteoblast differentiation. GATA4 was abundantly expressed in preosteoblast cells and gradually down-regulated during osteoblast differentiation. Overexpression of GATA4 in osteoblastic cells inhibited alkaline phosphatase activity and nodule formation in osteogenic conditioned cell culture system. In addition, overexpression of GATA4 attenuated expression of osteogenic marker genes, including Runx2, alkaline phosphatase, bone sialoprotein, and osteocalcin, all of which are important for osteoblast differentiation and function. Overexpression of GATA4 attenuated Runx2 promoter activity, whereas silencing of GATA4 increased Runx2 induction. We found that GATA4 interacted with Dlx5 and subsequently decreased Dlx5 binding activity to Runx2 promoter region. Our data suggest that GATA4 acts as a negative regulator in osteoblast differentiation by downregulation of Runx2. BMB Reports 2014; 47(8): 463-468] |
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