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Academic Background

Associate Professor of Biological Chemistry, Harvard Medical School, Boston

Senior Research Associate, Department of Orthopaedic Surgery, Children's Hospital Medical Center, Boston

Post-doctoral training: National Institutes of Health; Harvard Medical School, Children's Hospital.

Ph.D., Boston University School of Medicine

Molecular Mechanisms Regulating Skeletal Development and Metastasis of Cancer Cells to Bone

Bone tissue functions as a mechanically responsive structural component of the body and as a major organ essential for maintaining calcium and phosphate homeostasis. The skeleton is the target of numerous human genetic disorders and recently mouse models have identified new regulatory pathways that affect the skeleton. As a normal process of aging and hormonal changes after the menopause, skeletal mass can decrease by as much as 30% leading to bone fracture and compromised quality of life in the elderly population. Historically the laboratory has addressed molecular mechanisms regulating formation and mineralization of bone by osteoblasts and turnover of bone tissue by osteoclasts, the bone resorbing cells. We are defining the key regulatory events for the progressive differentiation of osteoprogenitor stem cells to osteogenic cells by identifying transcription factor complexes that control expression of tissue-specific genes. Our studies are showing that early events of skeletal development are recapitulated in the adult skeleton for the normal maintenance of bone mass.

The skeleton is also a target of metastatic cancers and recent studies from our laboratory and others are demonstrating that signaling pathways which mediate responsiveness of the bone forming and bone resorbing cells of the skeleton for organogenesis are also pathways that are activated in cancer cells which metastasize to bone.

Areas of current investigation for graduate and MD/PhD students and postdoctoral fellows include:

1.   Combinatorial Control Mechanisms for Skeletal Development

This laboratory is defining a regulatory network of developmental factors with a focus on three major pathways critical for skeletal pattern formation, early embryonic bone development, and osteoblast differentiation:  the bone morphogenetic protein (BMP) family, the Wnt signaling pathway and Hox homeodomain factors.  The integration of these signaling pathways for tissue-specific gene expression is being characterized for two genes, the transcription factor Runx2/Cbfa1 established as essential for skeletal development and a bone-specific Runx2 target gene, osteocalcin, that represents one of the major non-collagenous bone matrix proteins (Choi et al., 2001; Lengner et al., 2002).  The Runx2/Cbfa transcription factor is essential for osteogenic differentiation and functions as a master regulatory gene through multiple properties (Fig. 1). Runx2 can change the phenotype of a cell, e.g., from a non-osseous adipocyte to an osteoblast, as well as control recruitment of stem cells into the chondrogenic and osteogenic phenotype (Lengner et al., 2005).  Characterizing the functional activities of this protein has provided new paradigms for understanding gene regulation.  First, Runx2 expression is regulated in stem cells by early development cues including Hox genes, BMP/TGFb, and Wnt proteins (Balint et al., 2003, Zaidi et al., 2002; Gaur et al., 2005, 2006; Bodine et al., 2004).  Secondly, this transcription factor is a scaffolding protein that is targeted to specific subnuclear domains for the assembly of multimeric complexes on target genes (reviewed in Lian et al., 2004).  Third, Runx2 recruits chromatin remodeling proteins and assembles complexes at Runx2 regulatory elements in genes to either activate or repress gene transcription (Javed et al., 1999; Young et al., 2005).  By mutational analyses of different protein interacting domains of Runx2, we are identifying the coregulatory proteins essential for osteoblast differentiation in vitro and for skeletal development in vivo (Zaidi et al., 2004; Afzal et al., 2005). Experimental approaches include cell culture models for chondrocyte and osteoblast differentiation using human embryonic and mesenchymal stem cells, gene regulation studies and characterization of mouse phenotypes. 

2.  Tissue Specific Gene Regulatory Mechanisms

The osteocalcin gene encodes a calcium binding ECM protein that is developmentally regulated during bone formation by a plethora of hormones, growth factors, and cell signaling proteins involved in calcium homeostasis and bone remodeling. The integration of independent signals must converge on the promoter to account for complex physiologic control of the gene during bone formation and turnover. Thus, the promoter of the osteocalcin gene provides a molecular blueprint for understanding developmental and hormonal regulation of gene expression required for bone formation (Hassan et al., 2004; Javed et al., 1999; Gutierrez et al., 2004). Identification of tissue-specific regulatory sequences and their cognate binding factors have allowed us to develop strategies for cell based therapy to target therapeutic genes specifically to bone. Examples of osteocalcin tissue-specific regulatory elements undergoing characterization include the steroid response elements, runt homology (Runx/Cbfa), homeodomain (HD), Hox, C/EBP, ATF and AP-1 protein binding sites.  The HD proteins (Msx, Dlx) and Hoxa10 regulate osteocalcin at different stages of cell differentiation (Fig. 2). Transcriptional control of the gene is evaluated at multiple levels including chromatin modifications and recruitment of transcription factors and their coregulatory proteins by chromatin immunoprecipitation studies.  Enforced expression and siRNA knockdown studies of regulatory factors strategies are used to establish their function in vitro and in vivo using transgenic mouse models. Such analyses have revealed new insights into understanding the complex interplay of physiologic mediators of tissue differentiation. This program of research provides a student with fundamental techniques requisite for characterizing gene regulation and expression in a biological context.

3.  Cancer Cell Biology in the Bone Microenvironment

The end stage of breast and prostate cancer is metastasis to bone, with very poor prognosis with nearly 70% mortality within a year.  Cancer cells cause destruction of the bone, resulting in fractures and severe pain.  Understanding the mechanisms which induce metastasis of the primary cancer cell to the bone environment needs to be addressed.  We have identified high expression levels of the Runx2 transcription factor in metastatic breast and prostate cancer cell lines.  Runx target genes in the cancer cell include the entire class of matrix metalloproteinases characterized for their role in tissue invasion, the vascular endothelial growth factor, a potent angiogenic factor involved as a primary event in tumor growth and several cell growth and osteoblastic genes expressed in the bone environment that allow for tumor growth (Fig. 3) (Pratap et al., 2005).  The cancer cell responds to TGFb and BMP growth factors in the bone extracellular matrix and stimulates bone resorbing cells.  In recent studies, we have shown metastatic cancer cell lines in which Runx2 activity has been blocked through genetic mutations, that the osteolytic disease of breast cancer cells can be prevented in the mouse (Barnes et al., 2004; Javed et al., 2005). The presence of mutant Runx2 protein in metastatic cells inhibits cell invasion (in vitro assays) and genes associated with tumor growth (Fig. 3).  We are now turning our attention to mechanisms responsible for activation of Runx2 in the primary tumor that would lead to the metastatic event in vivo.  Experimental approaches include generation of human cancer cell lines with mutants of Runx2, assessing tumor growth by in vivo imaging of tumors in breast, prostate and bone tissues, and examining gene expression profiles of the tumors are assayed.

4.  Gene Therapy and Tissue Engineering for Skeletal Diseases

Genetic disorders of the skeleton require expression of the normal proteins, specifically in bone cells.   Here the osteocalcin gene promoter provides the appropriate method for targeting expressed genes to mature osteoblasts.  Using OC-EGFP mice, we are characterizing a population of mesenchymal stem cells from these mice that differentiate into bone cells expressing GFP in donor mice.  Numerous donor mice carrying mutated genes that mimic human genetic disorders are available for addressing the critical number of mesenchymal stem cells differentiated to osteoblasts that can provide a sufficient level of normal protein to correct the skeletal disorder.  A second example where tissue engineering is being developed relates to the problem of non-union fractures where scar tissue rather than new bone formation occurs.  By using autologous cells expressing osteogenic factors, bone formation can be induced.  Lastly, we are culturing human embryonic stem cells and promoting their differentiation to chondrogenic and osteogenic lineages and testing these in mouse models.  These powerful properties are being exploited for treatment of skeletal diseases that require rebuilding of skeletal tissue by promoting lineage allocation of stem cells or marrow progenitor cells. 

Figures

 Figure 1

 

  Lian Figure 1

 Figure 2

 

  Lian Figure 2
  

 Figure 3

 

  Lian Figure 3
  

 


One or more keywords matched the following items that are connected to Lian, Jane

Item TypeName
Academic Article CCAAT/enhancer-binding proteins (C/EBP) beta and delta activate osteocalcin gene transcription and synergize with Runx2 at the C/EBP element to regulate bone-specific expression.
Academic Article Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites.
Academic Article Identification of novel protein/DNA interactions within the promoter of the bone-related transcription factor Runx2/Cbfa1.
Academic Article Activation of the bone-related Runx2/Cbfa1 promoter in mesenchymal condensations and developing chondrocytes of the axial skeleton.
Academic Article Transcription factors RUNX1/AML1 and RUNX2/Cbfa1 dynamically associate with stationary subnuclear domains.
Academic Article Intranuclear trafficking of transcription factors: Requirements for vitamin D-mediated biological control of gene expression.
Academic Article Phenotype discovery by gene expression profiling: mapping of biological processes linked to BMP-2-mediated osteoblast differentiation.
Academic Article Intranuclear organization of RUNX transcriptional regulatory machinery in biological control of skeletogenesis and cancer.
Academic Article Runx2/Cbfa1 functions: diverse regulation of gene transcription by chromatin remodeling and co-regulatory protein interactions.
Academic Article Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts.
Academic Article Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription.
Academic Article Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression.
Academic Article Primary mouse embryonic fibroblasts: a model of mesenchymal cartilage formation.
Academic Article Analysis of in vivo gene expression using epitope-tagged proteins.
Academic Article Protein-deoxyribonucleic acid interactions linked to gene expression: ligation-mediated polymerase chain reaction.
Academic Article Intranuclear trafficking: organization and assembly of regulatory machinery for combinatorial biological control.
Academic Article The vitamin D response element in the distal osteocalcin promoter contributes to chromatin organization of the proximal regulatory domain.
Academic Article Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development.
Academic Article Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription.
Academic Article Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo.
Academic Article Nkx3.2-mediated repression of Runx2 promotes chondrogenic differentiation.
Academic Article Point mutation in AML1 disrupts subnuclear targeting, prevents myeloid differentiation, and effects a transformation-like phenotype.
Academic Article Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes.
Academic Article Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression.
Academic Article Combinatorial organization of the transcriptional regulatory machinery in biological control and cancer.
Academic Article Subnuclear targeting of Runx1 is required for synergistic activation of the myeloid specific M-CSF receptor promoter by PU.1.
Academic Article Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced chondrocyte differentiation.
Academic Article Alterations in intranuclear localization of Runx2 affect biological activity.
Academic Article Networks and hubs for the transcriptional control of osteoblastogenesis.
Academic Article Mitotic control of RUNX2 phosphorylation by both CDK1/cyclin B kinase and PP1/PP2A phosphatase in osteoblastic cells.
Academic Article Temporal evolution of gene expression in rat carotid artery following balloon angioplasty.
Academic Article Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2.
Academic Article Chromatin remodeling by SWI/SNF results in nucleosome mobilization to preferential positions in the rat osteocalcin gene promoter.
Academic Article HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes.
Academic Article Phosphorylation at serine 208 of the 1alpha,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators.
Academic Article Cooperation between p27 and p107 during endochondral ossification suggests a genetic pathway controlled by p27 and p130.
Academic Article Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220(NPAT) in human embryonic stem cells.
Academic Article Nucleosome organization and targeting of SWI/SNF chromatin-remodeling complexes: contributions of the DNA sequence.
Academic Article Cell cycle related modulations in Runx2 protein levels are independent of lymphocyte enhancer-binding factor 1 (Lef1) in proliferating osteoblasts.
Academic Article Structural coupling of Smad and Runx2 for execution of the BMP2 osteogenic signal.
Academic Article Phenotypic transcription factors epigenetically mediate cell growth control.
Academic Article Molecular consequences of a frameshifted DLX3 mutant leading to Tricho-Dento-Osseous syndrome.
Academic Article Expression of secreted frizzled related protein 1, a Wnt antagonist, in brain, kidney, and skeleton is dispensable for normal embryonic development.
Academic Article Runx2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors.
Academic Article Intricate gene regulatory networks of helix-loop-helix (HLH) proteins support regulation of bone-tissue related genes during osteoblast differentiation.
Academic Article Molecular switches involving homeodomain proteins, HOXA10 and RUNX2 regulate osteoblastogenesis.
Academic Article A microRNA signature for a BMP2-induced osteoblast lineage commitment program.
Academic Article Runx2 transcriptional activation of Indian Hedgehog and a downstream bone metastatic pathway in breast cancer cells.
Academic Article The histone gene cell cycle regulator HiNF-P is a unique zinc finger transcription factor with a novel conserved auxiliary DNA-binding motif.
Academic Article Altered chromatin modifications in AML1/RUNX1 breakpoint regions involved in (8;21) translocation.
Academic Article Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes.
Academic Article Co-stimulation of the bone-related Runx2 P1 promoter in mesenchymal cells by SP1 and ETS transcription factors at polymorphic purine-rich DNA sequences (Y-repeats).
Academic Article The subnuclear organization of histone gene regulatory proteins and 3' end processing factors of normal somatic and embryonic stem cells is compromised in selected human cancer cell types.
Academic Article Secreted frizzled related protein 1 is a target to improve fracture healing.
Academic Article The osteogenic transcription factor runx2 controls genes involved in sterol/steroid metabolism, including CYP11A1 in osteoblasts.
Academic Article Survival responses of human embryonic stem cells to DNA damage.
Academic Article The Notch-responsive transcription factor Hes-1 attenuates osteocalcin promoter activity in osteoblastic cells.
Academic Article Human embryonic stem cells are pre-mitotically committed to self-renewal and acquire a lengthened G1 phase upon lineage programming.
Academic Article Cyclin D2 and the CDK substrate p220(NPAT) are required for self-renewal of human embryonic stem cells.
Academic Article Expression of the osteoblast differentiation factor RUNX2 (Cbfa1/AML3/Pebp2alpha A) is inhibited by tumor necrosis factor-alpha.
Academic Article Definitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation.
Academic Article The cancer-related Runx2 protein enhances cell growth and responses to androgen and TGFbeta in prostate cancer cells.
Academic Article Transcriptional corepressor TLE1 functions with Runx2 in epigenetic repression of ribosomal RNA genes.
Academic Article A central dinucleotide within vitamin D response elements modulates DNA binding and transactivation by the vitamin D receptor in cellular response to natural and synthetic ligands.
Academic Article Genetic ablation of the CDP/Cux protein C terminus results in hair cycle defects and reduced male fertility.
Academic Article The human SWI/SNF complex associates with RUNX1 to control transcription of hematopoietic target genes.
Academic Article Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression.
Academic Article 1,25-(OH)2-vitamin D3 suppresses the bone-related Runx2/Cbfa1 gene promoter.
Academic Article Preclinical characterization of mitochondria-targeted small molecule hsp90 inhibitors, gamitrinibs, in advanced prostate cancer.
Academic Article Live cell imaging of the cancer-related transcription factor RUNX2 during mitotic progression.
Academic Article A network connecting Runx2, SATB2, and the miR-23a~27a~24-2 cluster regulates the osteoblast differentiation program.
Academic Article Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1.
Academic Article TIEG1/KLF10 modulates Runx2 expression and activity in osteoblasts.
Academic Article Epigenetic regulation of early osteogenesis and mineralized tissue formation by a HOXA10-PBX1-associated complex.
Academic Article Runx2 protein expression utilizes the Runx2 P1 promoter to establish osteoprogenitor cell number for normal bone formation.
Academic Article A RUNX2-HDAC1 co-repressor complex regulates rRNA gene expression by modulating UBF acetylation.
Academic Article Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene.
Academic Article miR-218 directs a Wnt signaling circuit to promote differentiation of osteoblasts and osteomimicry of metastatic cancer cells.
Academic Article Runx2 (Cbfa1, AML-3) interacts with histone deacetylase 6 and represses the p21(CIP1/WAF1) promoter.
Academic Article Multiple subnuclear targeting signals of the leukemia-related AML1/ETO and ETO repressor proteins.
Academic Article The core-binding factor beta subunit is required for bone formation and hematopoietic maturation.
Academic Article Cbfbeta interacts with Runx2 and has a critical role in bone development.
Academic Article Transcriptional induction of the osteocalcin gene during osteoblast differentiation involves acetylation of histones h3 and h4.
Academic Article Regulation of the bone-specific osteocalcin gene by p300 requires Runx2/Cbfa1 and the vitamin D3 receptor but not p300 intrinsic histone acetyltransferase activity.
Academic Article Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells.
Academic Article Runx1/AML1 hematopoietic transcription factor contributes to skeletal development in vivo.
Academic Article Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing.
Academic Article Temporal and spatial parameters of skeletal gene expression: targeting RUNX factors and their coregulatory proteins to subnuclear domains.
Academic Article Mitotic partitioning and selective reorganization of tissue-specific transcription factors in progeny cells.
Academic Article Nuclear microenvironments support assembly and organization of the transcriptional regulatory machinery for cell proliferation and differentiation.
Academic Article The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of trabecular bone formation in adult mice.
Academic Article Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors.
Academic Article The Runx2 transcription factor plays a key role in the 1alpha,25-dihydroxy Vitamin D3-dependent upregulation of the rat osteocalcin (OC) gene expression in osteoblastic cells.
Academic Article Fidelity of Runx2 activity in breast cancer cells is required for the generation of metastases-associated osteolytic disease.
Academic Article Immunofluorescence analysis using epitope-tagged proteins: in vitro system.
Academic Article Protein-deoxyribonucleic acid interactions linked to gene expression: electrophoretic mobility shift assay.
Academic Article Protein-deoxyribonucleic acid interactions linked to gene expression: DNase I digestion.
Academic Article Quantitative signature for architectural organization of regulatory factors using intranuclear informatics.
Academic Article Bone-specific transcription factor Runx2 interacts with the 1alpha,25-dihydroxyvitamin D3 receptor to up-regulate rat osteocalcin gene expression in osteoblastic cells.
Academic Article Dlx3 transcriptional regulation of osteoblast differentiation: temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene.
Academic Article SWI/SNF chromatin remodeling complex is obligatory for BMP2-induced, Runx2-dependent skeletal gene expression that controls osteoblast differentiation.
Academic Article The tyrosine phosphatase, OST-PTP, is expressed in mesenchymal progenitor cells early during skeletogenesis in the mouse.
Academic Article The dynamic organization of gene-regulatory machinery in nuclear microenvironments.
Academic Article The bone-specific expression of Runx2 oscillates during the cell cycle to support a G1-related antiproliferative function in osteoblasts.
Academic Article Organization of transcriptional regulatory machinery in osteoclast nuclei: compartmentalization of Runx1.
Academic Article The Wnt antagonist secreted frizzled-related protein-1 controls osteoblast and osteocyte apoptosis.
Academic Article Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype.
Academic Article Osteoblast differentiation and skeletal development are regulated by Mdm2-p53 signaling.
Academic Article Chromatin remodeling and transcriptional activity of the bone-specific osteocalcin gene require CCAAT/enhancer-binding protein beta-dependent recruitment of SWI/SNF activity.
Academic Article Reconstitution of Runx2/Cbfa1-null cells identifies a requirement for BMP2 signaling through a Runx2 functional domain during osteoblast differentiation.
Academic Article BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network.
Academic Article Establishment of histone gene regulation and cell cycle checkpoint control in human embryonic stem cells.
Academic Article Crystallization and preliminary X-ray analysis of a domain in the Runx2 transcription factor that interacts with the 1alpha,25 dihydroxy vitamin D3 receptor.
Academic Article 1alpha,25-dihydroxy vitamin D3-enhanced expression of the osteocalcin gene involves increased promoter occupancy of basal transcription regulators and gradual recruitment of the 1alpha,25-dihydroxy vitamin D3 receptor-SRC-1 coactivator complex.
Academic Article The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism.
Academic Article Specific residues of RUNX2 are obligatory for formation of BMP2-induced RUNX2-SMAD complex to promote osteoblast differentiation.
Academic Article Staged assembly of histone gene expression machinery at subnuclear foci in the abbreviated cell cycle of human embryonic stem cells.
Academic Article The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes.
Academic Article Sustained and localized in vitro release of BMP-2/7, RANKL, and tetracycline from FlexBone, an elastomeric osteoconductive bone substitute.
Academic Article SWI/SNF-independent nuclease hypersensitivity and an increased level of histone acetylation at the P1 promoter accompany active transcription of the bone master gene Runx2.
Academic Article The histone gene activator HINFP is a nonredundant cyclin E/CDK2 effector during early embryonic cell cycles.
Academic Article Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network.
Academic Article 1alpha,25-dihydroxy vitamin D(3) induces nuclear matrix association of the 1alpha,25-dihydroxy vitamin D(3) receptor in osteoblasts independently of its ability to bind DNA.
Academic Article Recruitment and subnuclear distribution of the regulatory machinery during 1alpha,25-dihydroxy vitamin D3-mediated transcriptional upregulation in osteoblasts.
Academic Article The cleidocranial dysplasia-related R131G mutation in the Runt-related transcription factor RUNX2 disrupts binding to DNA but not CBF-beta.
Academic Article Pbx1 represses osteoblastogenesis by blocking Hoxa10-mediated recruitment of chromatin remodeling factors.
Academic Article Subnuclear localization and intranuclear trafficking of transcription factors.
Academic Article Architectural epigenetics: mitotic retention of mammalian transcriptional regulatory information.
Academic Article Reprogramming the pluripotent cell cycle: restoration of an abbreviated G1 phase in human induced pluripotent stem (iPS) cells.
Academic Article An architectural genetic and epigenetic perspective.
Academic Article C/EBPß binds the P1 promoter of the Runx2 gene and up-regulates Runx2 transcription in osteoblastic cells.
Academic Article Bookmarking the genome: maintenance of epigenetic information.
Academic Article Functional coupling of transcription factor HiNF-P and histone H4 gene expression during pre- and post-natal mouse development.
Academic Article TRAP-1, the mitochondrial Hsp90.
Academic Article Resolution of inflammation induces osteoblast function and regulates the Wnt signaling pathway.
Academic Article Genomic promoter occupancy of runt-related transcription factor RUNX2 in Osteosarcoma cells identifies genes involved in cell adhesion and motility.
Academic Article Neural crest deletion of Dlx3 leads to major dentin defects through down-regulation of Dspp.
Academic Article Runx2 mediates epigenetic silencing of the bone morphogenetic protein-3B (BMP-3B/GDF10) in lung cancer cells.
Academic Article Epigenetic mechanisms in leukemia.
Academic Article In vivo impact of Dlx3 conditional inactivation in neural crest-derived craniofacial bones.
Academic Article Conditional inactivation of the mouse Wwox tumor suppressor gene recapitulates the null phenotype.
Academic Article Runx2 protein represses Axin2 expression in osteoblasts and is required for craniosynostosis in Axin2-deficient mice.
Academic Article Oncogenic cooperation between PI3K/Akt signaling and transcription factor Runx2 promotes the invasive properties of metastatic breast cancer cells.
Academic Article MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma.
Concept Proto-Oncogene Protein c-ets-1
Concept Parathyroid Hormone-Related Protein
Concept Membrane Proteins
Concept Receptor-Like Protein Tyrosine Phosphatases, Class 3
Concept Protein Binding
Concept Protein Subunits
Concept Protein Transport
Concept DNA-Binding Proteins
Concept Oncogene Proteins, Fusion
Concept Matrix Attachment Region Binding Proteins
Concept Protein Folding
Concept CCAAT-Enhancer-Binding Protein-alpha
Concept Protein Processing, Post-Translational
Concept Tumor Suppressor Protein p14ARF
Concept Tumor Suppressor Protein p53
Concept Bone Morphogenetic Protein 7
Concept Mitogen-Activated Protein Kinases
Concept Retinoblastoma-Like Protein p107
Concept High Mobility Group Proteins
Concept Smad5 Protein
Concept Hedgehog Proteins
Concept Carrier Proteins
Concept Chromosomal Proteins, Non-Histone
Concept Cell Cycle Proteins
Concept Luminescent Proteins
Concept Protein Biosynthesis
Concept Receptors, G-Protein-Coupled
Concept CDC2 Protein Kinase
Concept Nuclear Proteins
Concept Retinoblastoma-Like Protein p130
Concept Recombinant Proteins
Concept Protein Interaction Domains and Motifs
Concept Mutant Proteins
Concept Protein-Serine-Threonine Kinases
Concept Pol1 Transcription Initiation Complex Proteins
Concept Extracellular Matrix Proteins
Concept Smad Proteins
Concept Protein Synthesis Inhibitors
Concept Proto-Oncogene Proteins c-mdm2
Concept CCAAT-Enhancer-Binding Protein-delta
Concept Intercellular Signaling Peptides and Proteins
Concept Repressor Proteins
Concept HSP90 Heat-Shock Proteins
Concept MyoD Protein
Concept CCAAT-Enhancer-Binding Protein-beta
Concept Bone Morphogenetic Proteins
Concept Proto-Oncogene Proteins c-akt
Concept Nuclear Matrix-Associated Proteins
Concept Proteins
Concept Microtubule-Associated Proteins
Concept Homeodomain Proteins
Concept Cytoskeletal Proteins
Concept Protein Structure, Tertiary
Concept Follistatin-Related Proteins
Concept Protein Multimerization
Concept Co-Repressor Proteins
Concept Myeloid-Lymphoid Leukemia Protein
Concept Green Fluorescent Proteins
Concept Recombinant Fusion Proteins
Concept Inhibitor of Apoptosis Proteins
Concept Protein Stability
Concept Protein Tyrosine Phosphatases
Concept Saccharomyces cerevisiae Proteins
Concept Proto-Oncogene Proteins c-jun
Concept Neoplasm Proteins
Concept CCAAT-Enhancer-Binding Proteins
Concept Wnt Proteins
Concept Protein Sorting Signals
Concept Protein Isoforms
Concept Bone Morphogenetic Protein 2
Concept Proto-Oncogene Proteins
Concept Mitogen-Activated Protein Kinase Phosphatases
Concept Tumor Suppressor Proteins
Concept RNA-Binding Proteins
Academic Article Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.
Academic Article Integrin avß6 promotes an osteolytic program in cancer cells by upregulating MMP2.
Academic Article Bookmarking target genes in mitosis: a shared epigenetic trait of phenotypic transcription factors and oncogenes?
Academic Article Epigenetic landscape during osteoblastogenesis defines a differentiation-dependent Runx2 promoter region.
Academic Article A functional N-terminal domain in C/EBPß-LAP* is required for interacting with SWI/SNF and to repress Ric-8B gene transcription in osteoblasts.
Academic Article Core binding factor ß (CBFß) is retained in the midbody during cytokinesis.
Academic Article Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice.
Academic Article Subnuclear domain proteins in cancer cells support the functions of RUNX2 in the DNA damage response.
Academic Article Fidelity of histone gene regulation is obligatory for genome replication and stability.
Academic Article microRNA-mediated survivin control of pluripotency.
Academic Article Runx2-Smad signaling impacts the progression of tumor-induced bone disease.
Academic Article CBFß and the leukemogenic fusion protein CBFß-SMMHC associate with mitotic chromosomes to epigenetically regulate ribosomal genes.
Academic Article Targeting of Runx2 by miR-135 and miR-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease.
Academic Article Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells.
Academic Article Expression of the IL-11 Gene in Metastatic Cells Is Supported by Runx2-Smad and Runx2-cJun Complexes Induced by TGFß1.
Academic Article p53 checkpoint ablation exacerbates the phenotype of Hinfp dependent histone H4 deficiency.
Academic Article The SWI/SNF ATPases Are Required for Triple Negative Breast Cancer Cell Proliferation.
Academic Article Epigenetic Control of the Bone-master Runx2 Gene during Osteoblast-lineage Commitment by the Histone Demethylase JARID1B/KDM5B.
Academic Article Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation.
Academic Article Epigenetic Modulation in Periodontitis: Interaction of Adiponectin and JMJD3-IRF4 Axis in Macrophages.
Academic Article Expression of Ribosomal RNA and Protein Genes in Human Embryonic Stem Cells Is Associated With the Activating H3K4me3 Histone Mark.

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