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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

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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 Identification of novel protein/DNA interactions within the promoter of the bone-related transcription factor Runx2/Cbfa1.
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 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 Nuclear microenvironments support physiological control of gene expression.
Academic Article Cell growth regulatory role of Runx2 during proliferative expansion of preosteoblasts.
Academic Article Functional architecture of the nucleus: organizing the regulatory machinery for gene expression, replication and repair.
Academic Article Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression.
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 Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo.
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 Lymphocyte enhancer-binding factor 1 (Lef1) inhibits terminal differentiation of osteoblasts.
Academic Article Secreted frizzled related protein 1 regulates Wnt signaling for BMP2 induced chondrocyte differentiation.
Academic Article An architectural perspective of cell-cycle control at the G1/S phase cell-cycle transition.
Academic Article Networks and hubs for the transcriptional control of osteoblastogenesis.
Academic Article Temporal evolution of gene expression in rat carotid artery following balloon angioplasty.
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 Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2.
Academic Article Organization of transcriptional regulatory machinery in nuclear microenvironments: implications for biological control and cancer.
Academic Article Cell cycle dependent phosphorylation and subnuclear organization of the histone gene regulator p220(NPAT) in human embryonic stem cells.
Academic Article Nuclear microenvironments in biological control and cancer.
Academic Article Vitamin D control of gene expression: temporal and spatial parameters for organization of the regulatory machinery.
Academic Article Phenotypic transcription factors epigenetically mediate cell growth control.
Academic Article Chromatin immunoprecipitation assays: application of ChIP-on-chip for defining dynamic transcriptional mechanisms in bone cells.
Academic Article Molecular consequences of a frameshifted DLX3 mutant leading to Tricho-Dento-Osseous syndrome.
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 osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts.
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 Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation.
Academic Article The osteogenic transcription factor runx2 controls genes involved in sterol/steroid metabolism, including CYP11A1 in osteoblasts.
Academic Article Prostate cancer regulatory networks.
Academic Article The Notch-responsive transcription factor Hes-1 attenuates osteocalcin promoter activity in osteoblastic cells.
Academic Article Ectopic runx2 expression in mammary epithelial cells disrupts formation of normal acini structure: implications for breast cancer progression.
Academic Article Transcription factor-mediated epigenetic regulation of cell growth and phenotype for biological control and cancer.
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 The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of Runx2 in skeletal tissues.
Academic Article The human SWI/SNF complex associates with RUNX1 to control transcription of hematopoietic target genes.
Academic Article Reduced CpG methylation is associated with transcriptional activation of the bone-specific rat osteocalcin gene in osteoblasts.
Academic Article 1,25-(OH)2-vitamin D3 suppresses the bone-related Runx2/Cbfa1 gene promoter.
Academic Article A network connecting Runx2, SATB2, and the miR-23a~27a~24-2 cluster regulates the osteoblast differentiation program.
Academic Article Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility.
Academic Article Architectural genetic and epigenetic control of regulatory networks: compartmentalizing machinery for transcription and chromatin remodeling in nuclear microenvironments.
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 The abbreviated pluripotent cell cycle.
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 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 MicroRNA functions in osteogenesis and dysfunctions in osteoporosis.
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 Nuclear microenvironments support assembly and organization of the transcriptional regulatory machinery for cell proliferation and differentiation.
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 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 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 The Runx2 osteogenic transcription factor regulates matrix metalloproteinase 9 in bone metastatic cancer cells and controls cell invasion.
Academic Article The bone-related Zn finger transcription factor Osterix promotes proliferation of mesenchymal cells.
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 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 The 1alpha,25-dihydroxy Vitamin D3 receptor preferentially recruits the coactivator SRC-1 during up-regulation of the osteocalcin gene.
Academic Article An architectural perspective of vitamin D responsiveness.
Academic Article Targeted deletion of Wwox reveals a tumor suppressor function.
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 In situ nuclear organization of regulatory machinery.
Academic Article The WWOX tumor suppressor is essential for postnatal survival and normal bone metabolism.
Academic Article Genetic and epigenetic regulation in nuclear microenvironments for biological control in cancer.
Academic Article Targeted ablation of the WW domain-containing oxidoreductase tumor suppressor leads to impaired steroidogenesis.
Academic Article Enhanced fracture repair by leukotriene antagonism is characterized by increased chondrocyte proliferation and early bone formation: a novel role of the cysteinyl LT-1 receptor.
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 Impaired cell cycle regulation of the osteoblast-related heterodimeric transcription factor Runx2-Cbfbeta in osteosarcoma cells.
Academic Article Recruitment and subnuclear distribution of the regulatory machinery during 1alpha,25-dihydroxy vitamin D3-mediated transcriptional upregulation in osteoblasts.
Academic Article Pbx1 represses osteoblastogenesis by blocking Hoxa10-mediated recruitment of chromatin remodeling factors.
Academic Article Metastatic bone disease: role of transcription factors and future targets.
Academic Article Architectural epigenetics: mitotic retention of mammalian transcriptional regulatory information.
Academic Article A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes.
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 Suberoylanilide hydroxamic acid (SAHA; vorinostat) causes bone loss by inhibiting immature osteoblasts.
Academic Article C/EBP? binds the P1 promoter of the Runx2 gene and up-regulates Runx2 transcription in osteoblastic cells.
Academic Article Functional coupling of transcription factor HiNF-P and histone H4 gene expression during pre- and post-natal mouse development.
Academic Article A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2.
Academic Article Neural crest deletion of Dlx3 leads to major dentin defects through down-regulation of Dspp.
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 MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma.
Concept Down-Regulation
Concept Up-Regulation
Concept Gene Expression Regulation, Leukemic
Concept Gene Expression Regulation, Developmental
Concept Gene Expression Regulation
Concept Gene Expression Regulation, Enzymologic
Concept Gene Expression Regulation, Neoplastic
Academic Article Genomic occupancy of Runx2 with global expression profiling identifies a novel dimension to control of osteoblastogenesis.
Academic Article A germline point mutation in Runx1 uncouples its role in definitive hematopoiesis from differentiation.
Academic Article Integrin av?6 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 A functional N-terminal domain in C/EBP?-LAP* is required for interacting with SWI/SNF and to repress Ric-8B gene transcription in osteoblasts.
Academic Article MicroRNAs in the control of metastatic bone disease.
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 Fidelity of histone gene regulation is obligatory for genome replication and stability.
Academic Article microRNA-mediated survivin control of pluripotency.
Academic Article CBF? and the leukemogenic fusion protein CBF?-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 Expression of the IL-11 Gene in Metastatic Cells Is Supported by Runx2-Smad and Runx2-cJun Complexes Induced by TGF?1.
Academic Article The SWI/SNF ATPases Are Required for Triple Negative Breast Cancer Cell Proliferation.
Academic Article Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells.
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 Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause.
Academic Article Thyroid Hormone Receptor-? (TR?) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A Novel Signaling Pathway in Thyroid Cancer.
Academic Article MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple-negative MDA-MB-231 human breast cancer cells.
Academic Article SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells.
Academic Article Dissection of Individual Prostate Lobes in Mouse Models of Prostate Cancer to Obtain High Quality RNA.
Academic Article Transient RUNX1 Expression during Early Mesendodermal Differentiation of?hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling.
Academic Article RUNX1 contributes to higher-order chromatin organization and gene regulation in breast cancer cells.
Academic Article Maternal expression and early induction of histone gene transcription factor Hinfp sustains development in pre-implantation embryos.
Academic Article Identifying Nuclear Matrix-Attached DNA Across the Genome.
Academic Article Ethanol Extract of Cissus quadrangularis Enhances Osteoblast Differentiation and Mineralization of Murine Pre-Osteoblastic MC3T3-E1 Cells.
Academic Article Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis.
Academic Article Precocious Phenotypic Transcription-Factor Expression During Early Development.
Academic Article A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice.
Academic Article Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition.
Academic Article Selective expression of long non-coding RNAs in a breast cancer cell progression model.
Academic Article Intranuclear and higher-order chromatin organization of the major histone gene cluster in breast cancer.
Academic Article An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells.
Academic Article Bivalent Epigenetic Control of Oncofetal Gene Expression in Cancer.
Academic Article Genome-wide DNase hypersensitivity, and occupancy of RUNX2 and CTCF reveal a highly dynamic gene regulome during MC3T3 pre-osteoblast differentiation.
Academic Article Suppression of Breast Cancer Stem Cells and Tumor Growth by the RUNX1 Transcription Factor.
Academic Article Loss of RUNX1 is associated with aggressive lung adenocarcinomas.
Academic Article Mll-COMPASS complexes mediate H3K4me3 enrichment and transcription of the osteoblast master gene Runx2/p57 in osteoblasts.
Academic Article Regulation of Bone Metabolism by Serotonin.
Academic Article Higher order genomic organization and regulatory compartmentalization for cell cycle control at the G1/S-phase transition.
Academic Article Regulation of osteogenesis by long noncoding RNAs: An epigenetic mechanism contributing to bone formation.
Academic Article Thyroid Hormone Receptor ? Suppression of RUNX2 Is Mediated by Brahma-Related Gene 1-Dependent Chromatin Remodeling.
Academic Article Osteocalcin gene promoter: Unlocking the secrets for regulation of osteoblast growth and differentiation.
Academic Article Mitotically-Associated lncRNA (MANCR) Affects Genomic Stability and Cell Division in Aggressive Breast Cancer.
Academic Article Ethyl acetate and n-butanol fraction of Cissus quadrangularis promotes the mineralization potential of murine pre-osteoblast cell line MC3T3-E1 (sub-clone 4).
Academic Article RUNX1-dependent mechanisms in biological control and dysregulation in cancer.
Academic Article Osteogenic potential of hexane and dichloromethane fraction of Cissus quadrangularis on murine preosteoblast cell line MC3T3-E1 (subclone 4).
Academic Article Correction: Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation.
Academic Article Switches in histone modifications epigenetically control vitamin D3-dependent transcriptional upregulation of the CYP24A1 gene in osteoblastic cells.
Academic Article Ezh2-dependent H3K27me3 modification dynamically regulates vitamin D3-dependent epigenetic control of CYP24A1 gene expression in osteoblastic cells.
Academic Article Identification of tRNA-derived small RNA (tsRNA) responsive to the tumor suppressor, RUNX1, in breast cancer.
Academic Article RUNX1 and RUNX2 transcription factors function in opposing roles to regulate breast cancer stem cells.
Academic Article Bioactivity-Guided Isolation and Identification of Anti-adipogenic Constituents from the n-Butanol Fraction of Cissus quadrangularis.
Academic Article Epigenetic-Mediated Regulation of Gene Expression for Biological Control and Cancer: Cell and Tissue Structure, Function, and Phenotype.
Academic Article Epigenetic-Mediated Regulation of Gene Expression for Biological Control and Cancer: Fidelity of Mechanisms Governing the Cell Cycle.
Academic Article Bromodomain Proteins Epigenetically Regulate the Mitotically Associated lncRNA MANCR in Triple Negative Breast Cancer Cells.
Academic Article RUNX2 as a Prognostic Factor in Human Cancers.
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