GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2
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Osteoblasts are specialized mesenchymal cells that areresponsible for bone formation. In this study, we examine therole of GATA4 in osteoblast differentiation. GATA4 wasabundantly expressed in preosteoblast cells and graduallydown-regulated during osteoblast differentiation. Overexpressionof GATA4 in osteoblastic cells inhibited alkalinephosphatase activity and nodule formation in osteogenicconditioned cell culture system. In addition, overexpressionof GATA4 attenuated expression of osteogenic marker genes,including Runx2, alkaline phosphatase, bone sialoprotein,and osteocalcin, all of which are important for osteoblastdifferentiation and function. Overexpression of GATA4attenuated Runx2 promoter activity, whereas silencing ofGATA4 increased Runx2 induction. We found that GATA4interacted with Dlx5 and subsequently decreased Dlx5binding activity to Runx2 promoter region. Our data suggestthat GATA4 acts as a negative regulator in osteoblastdifferentiation by downregulation of Runx2.
Abstract
Osteoblasts are specialized mesenchymal cells that areresponsible for bone formation. In this study, we examine therole of GATA4 in osteoblast differentiation. GATA4 wasabundantly expressed in preosteoblast cells and graduallydown-regulated during osteoblast differentiation. Overexpressionof GATA4 in osteoblastic cells inhibited alkalinephosphatase activity and nodule formation in osteogenicconditioned cell culture system. In addition, overexpressionof GATA4 attenuated expression of osteogenic marker genes,including Runx2, alkaline phosphatase, bone sialoprotein,and osteocalcin, all of which are important for osteoblastdifferentiation and function. Overexpression of GATA4attenuated Runx2 promoter activity, whereas silencing ofGATA4 increased Runx2 induction. We found that GATA4interacted with Dlx5 and subsequently decreased Dlx5binding activity to Runx2 promoter region. Our data suggestthat GATA4 acts as a negative regulator in osteoblastdifferentiation by downregulation of Runx2.
참고문헌 (21)
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