Interrelationship of RUNX2 and estrogen pathway in skeletal tissues

Department of Biochemistry and Cell Biology, School of Medicine, WCU Program, Kyungpook National University, Daegu, Korea.
BMB reports (Impact Factor: 2.6). 10/2011; 44(10):613-8. DOI: 10.5483/BMBRep.2011.44.10.613
Source: PubMed


Two key molecules in skeletal tissues are bone formation master transcription factor Runx2 and the steroid hormone estrogen. It is well known that these two molecules play pivotal roles in bone homeostasis; however, the functional interaction between Runx2 and estrogen synthesis in skeletal tissues is largely unknown. Recent studies have indicated that there is a positive relationship between Runx2 and the estrogen biosynthesis pathway. In this review, a possible functional link between Runx2 and estrogen synthesis pathway in skeletal tissues will be discusses as well as the biological significance of this interaction.

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    • "In vitro studies have shown that ERα directly interacts with, and inhibits runx2 in the presence of 17β-estrogen [3] [5]. These positive and negative interactions are likely to be vital in estrogendeficient environments [3] [11]. More work needs to be done to characterise the interaction between ERα36 and Runx2 and its functional role in osteogenic differentiation. "

    Full-text · Dataset · Jan 2015
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    • "Apart from skeletal tissues and teeth, RUNX2 is also expressed in a number of other tissues, as ovary, testis, brain, and blood B cells ( Jeong et al., 2008; Cohen, 2009), and it may have other functions in these organs. One such function is modulation of the aromatase gene expression ( Jeong and Choi, 2011). The expression of RUNX2 in human hippocampus was also shown, and its lowered expression was attributed to patients with bipolar affective disorder, but the role of RUNX2 in this tissue is not completely known (Benes et al., 2007). "
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    ABSTRACT: RUNX2 is a member of the RUNX family of transcription factors, also containing the RUNX1 and RUNX3 proteins. These factors control the expression of genes essential for proper development in many cell lineages. RUNX2 plays a crucial role in the proliferation and differentiation of osteoblasts, required for bone formation. The cellular level of RUNX2 oscillates in a cell phase-specific manner, reaching a maximum at G2/M in some cells and overexpression of RUNX2 in osteoblasts blocked G1 to S phase progression. Recent studies have shown that RUNX2 may interact with p53 and change the activity of a histone deacetylase. Moreover, RUNX2 may act as an oncogene in cancer transformation, inevitably associated with genomic instability evoked by increased occurrence of DNA damage. We showed that some RUNX2 modifiers changed the sensitivity of differentiating preosteoblasts to DNA damage induced by oxidative stress. All these data suggest the involvement of RUNX2 in cellular DNA damage response (DDR), which is particularly important in osteogenesis as the process of osteoblast differentiation is associated with increasing oxidative stress. However, the mechanism underlying DDR involvement of RUNX2 is unknown. The basic question, whether RUNX2 plays a positive or destructive role in DDR in differentiating cells is still open.
    Full-text · Article · Jan 2015 · DNA and Cell Biology
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    • "Exogenous addition of FGF4 significantly diminished DAG-induced increases in the mRNA levels of Runx2 and osterix, but not of OC and BSP. Runx2 and osterix are essential osteoblast-specific transcription factors regulating bone differentiation [42], [43]. These factors activate a repertoire of genes during differentiation of pre-osteoblasts into mature osteoblasts and osteocytes [42], [44]. "
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    ABSTRACT: Fibroblast growth factor-4 (FGF4) is expressed in embryonic stages and in adult tissues, where it plays critical roles in modulating multiple cellular functions. However, the exact roles of FGF4 on proliferation and differentiation of embryonic stem cells (ESCs) are not completely understood. Exogenous addition of FGF4 stimulated proliferation of mouse ESCs (mESCs), as proven by the increases in DNA synthesis and cell cycle regulatory protein induction. These increases were almost completely inhibited by pre-treating cells with anti-FGF4 antibody. FGF4 also activated c-Jun N-terminal kinase (JNK) and extracellular-signal regulated kinase (ERK) signaling, but not p38 kinase. Blockage of JNK signaling by SP600125 or by transfection with its specific siRNA significantly inhibited FGF4-stimulated cell proliferation through the suppression of c-Jun induction and activator protein-1 (AP-1) activity. However, ERK or p38 kinase inhibitor did not affect FGF4-stimulated proliferation in mESCs. FGF4 suppressed osteogenic differentiation of mESCs by inhibiting expression of transcription factors involved in bone formation. Further, exogenous FGF4 addition stimulated proliferation of human periodontal ligament stem cells (hPDLSCs) and bone marrow mesenchymal stem cells (BMMSCs) via activation of ERK signaling. FGF4 also augmented mineralization of hPDLSCs, but not of BMMSCs. Collectively, it is suggested that FGF4 triggers proliferation of stem cells by activating MAPK-mediated signaling, while it affects differently osteogenic differentiation according to the origins of stem cells.
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