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Transcription Factor Runx2 (transcription + factor_runx2)
Selected AbstractsIdentification of Novel Target Genes of the Bone-Specific Transcription Factor Runx2,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2004Michael Stock Abstract Fifteen putative transcriptional target genes regulated by the osteogenic transcription factor Runx2 were identified by cDNA microarray and differential hybridization techniques. Expression pattern and regulation of one gene, Pttg1ip, was analyzed in detail. Introduction: The transcription factor Runx2 is a key regulator of osteoblast development and plays a role in chondrocyte maturation. The identification of transcriptional target genes of Runx2 may yield insight into how osteoblastic differentiation is achieved on a molecular level. Materials and Methods: Using a differential hybridization technique (selective amplification through biotin and restriction-mediated enrichment [SABRE]) and cDNA microarray analysis, 15 differentially expressed genes were identified using mRNA from C3H 10T1/2 cells with constitutive and inducible overexpression of Runx2. Results and Conclusions: Among the 15 genes identified, 4 encode the extracellular matrix proteins Ecm1, Mgp, Fbn5, and Osf-2, three represent the transcription factors Esx1, Osr1, and Sox9, whereas others were Ptn, Npdc-1, Hig1, and Tem1. The gene for Pttg1ip was upregulated in Runx2-expressing cells. Pttg1ip is widely expressed during development, but at highest levels in limbs and gonads. The Pttg1ip promoter binds Runx2 in a sequence specific manner, and Runx2 is able to transactivate the Pttg1ip promoter in MC3T3-E1 cells. Therefore, Pttg1ip is likely to be a novel direct transcriptional target gene of Runx2. In conclusion, the genes identified in this study are important candidates for mediating Runx2 induced cellular differentiation. [source] Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5GENES TO CELLS, Issue 10 2001Kyoko Shirakabe Background Runx2, formerly called PEBP2,A or Cbfa1, is a transcription factor whose deletion causes a complete lack of ossification. It directly regulates the expression of osteoblast-specific genes through the osteoblast-specific cis -acting element found in the promoter region of these genes. Results In this study, we have found conditions in which induction of the expression of Runx2 is not accompanied by expression of an osteoblast-specific gene, osteocalcin in C2C12 cells. This finding suggests the existence of a repressor of the activity of Runx2. We have then found that the homeobox protein Msx2 is able to repress the transcription activity of Runx2 by interacting with it. Furthermore, our results have shown that the other homeobox protein Dlx5 has an activity which interferes with both abilities of Msx2 to interact with Runx2 and repress its transcription activity. It has previously been shown that a missense mutation of Msx2 (P148H) causes Boston-type craniosynostosis in humans. Interestingly, while this mutant form of Msx2 was able to bind to Runx2 and repress its activity, these abilities of Msx2 (P148H) were not subject to regulation by Dlx5. Conclusion These results suggest that regulation of the activity of Runx2 by Msx2 and Dlx5 plays an important role in the mammalian skull development. [source] Identification of Novel Target Genes of the Bone-Specific Transcription Factor Runx2,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2004Michael Stock Abstract Fifteen putative transcriptional target genes regulated by the osteogenic transcription factor Runx2 were identified by cDNA microarray and differential hybridization techniques. Expression pattern and regulation of one gene, Pttg1ip, was analyzed in detail. Introduction: The transcription factor Runx2 is a key regulator of osteoblast development and plays a role in chondrocyte maturation. The identification of transcriptional target genes of Runx2 may yield insight into how osteoblastic differentiation is achieved on a molecular level. Materials and Methods: Using a differential hybridization technique (selective amplification through biotin and restriction-mediated enrichment [SABRE]) and cDNA microarray analysis, 15 differentially expressed genes were identified using mRNA from C3H 10T1/2 cells with constitutive and inducible overexpression of Runx2. Results and Conclusions: Among the 15 genes identified, 4 encode the extracellular matrix proteins Ecm1, Mgp, Fbn5, and Osf-2, three represent the transcription factors Esx1, Osr1, and Sox9, whereas others were Ptn, Npdc-1, Hig1, and Tem1. The gene for Pttg1ip was upregulated in Runx2-expressing cells. Pttg1ip is widely expressed during development, but at highest levels in limbs and gonads. The Pttg1ip promoter binds Runx2 in a sequence specific manner, and Runx2 is able to transactivate the Pttg1ip promoter in MC3T3-E1 cells. Therefore, Pttg1ip is likely to be a novel direct transcriptional target gene of Runx2. In conclusion, the genes identified in this study are important candidates for mediating Runx2 induced cellular differentiation. [source] Regulated expression of syndecan-4 in rat calvaria osteoblasts induced by fibroblast growth factor-2JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007Shu Jun Song Abstract Fibroblast growth factor-2 (FGF2) is a member of a prominent growth factor family that drives proliferation in a wide variety of cell types, including osteoblasts. The binding and signal transduction triggered by these mitogens is dependent on glycosaminoglycan (GAG) sugars, particularly of the heparan sulfate (HS) class. These are secreted in proteoglycan (PG) complexes, some of which become FGF co-receptors. The syndecans, the transmembrane forms of HSPG of which there are four members, act as multifunctional receptors for a variety of ligands involved in cell-extracellular matrix (ECM) adhesion as well as growth factor binding. To understand the role of syndecans in developing osteoblasts, the effects of exogenous FGF2 on syndecan expression were examined using primary rat calvarial osteoblasts. All four syndecan mRNAs were expressed in the osteoblasts, although only syndecan-4 was upregulated by FGF2 treatment in a dose-dependent manner. This upregulation could be abrogated by pretreatment with the protein synthesis inhibitor cycloheximide, suggesting that the upregulation of syndecan-4 by FGF2 is not a primary response. Osteoblast proliferation and mineralization were enhanced by exogenous FGF2 treatment, but could be specifically diminished by anti-syndecan-4 antibody pretreatment. This treatment also blocked FGF2-induced extracellular signal-regulated kinase activation, but not the expression of the bone-specific transcription factor Runx2. These results demonstrate that mitogen-triggered syndecan-4 expression is an intrinsic part of the pathways subtending osteoblast proliferation and mineralization. J. Cell. Biochem. 100: 402,411, 2007. © 2006 Wiley-Liss, Inc. [source] Prostate cancer expression of runt-domain transcription factor Runx2, a key regulator of osteoblast differentiation and functionTHE PROSTATE, Issue 1 2003Kristen D. Brubaker Abstract BACKGROUND Prostate cancer (CaP) bone metastases express numerous proteins associated with bone cells. Specific transcription factors, including Runx2, regulate the expression of many bone-related factors in osteoblasts. Expression of these transcription factors in CaP may be linked to the ability of CaP bone metastases to influence bone remodeling. METHODS CaP tissues and cell lines were analyzed for expression of Runx2 mRNA by RT-PCR and in situ hybridization, and protein by immunohistochemistry, Western blotting, and electrophoretic mobility shift assays (EMSA). RESULTS Runx2 mRNA and protein were detected in CaP tissues and cell lines. A specific Runx2: OSE2 complex could be formed with PC-3 nuclear extracts. CONCLUSIONS Expression of Runx2 in CaP may be the molecular switch that is associated with expression of various bone-specific factors in CaP. In turn, expression of these factors can influence bone remodeling and possibly play a role in the growth and survival of CaP in bone. Prostate 56: 13,22, 2003. © 2003 Wiley-Liss, Inc. [source] Polymethylmethacrylate particles impair osteoprogenitor viability and expression of osteogenic transcription factors Runx2, osterix, and Dlx5JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2010Richard Chiu Abstract Polymethylmethacrylate (PMMA) particles have been shown to inhibit the differentiation of osteoprogenitor cells, but the mechanism of this inhibitory effect has not been investigated. We hypothesize that the inhibitory effects of PMMA particles involve impairment of osteoprogenitor viability and direct inhibition of transcription factors that regulate osteogenesis. We challenged MC3T3-E1 osteoprogenitors with PMMA particles and examined the effects of these materials on osteoprogenitor viability and expression of transcription factors Runx2, osterix, Dlx5, and Msx2. MC3T3-E1 cells treated with PMMA particles over a 72-h period showed a significant reduction in cell viability and proliferation as indicated by a dose- and time-dependent increase in supernatant levels of lactate dehydrogenase, an intracellular enzyme released from dead cells, a dose-dependent decrease in cell number and BrdU uptake, and the presence of large numbers of positively labeled Annexin V-stained cells. The absence of apoptotic cells on TUNEL assay indicated that cell death occurred by necrosis, not apoptosis. MC3T3-E1 cells challenged with PMMA particles during the first 6 days of differentiation in osteogenic medium showed a significant dose-dependent decrease in the RNA expression of Runx2, osterix, and Dlx5 on all days of measurement, while the RNA expression of Msx2, an antagonist of Dlx5-induced osteogenesis, remained relatively unaffected. These results indicate that PMMA particles impair osteoprogenitor viability and inhibit the expression of transcription factors that promote osteoprogenitor differentiation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:571,577, 2010 [source] | |||||||||||||