A5063850442- Bone Metabolism and Diseases
- TGF-β signaling in diseases
- Genomics and Chromatin Dynamics
- Bone health and treatments
- RNA Research and Splicing
- Multiple Myeloma Research and Treatments
- Acute Myeloid Leukemia Research
- Cytokine Signaling Pathways and Interactions
- Chemokine receptors and signaling
- Bone and Dental Protein Studies
- S100 Proteins and Annexins
- Retinoids in leukemia and cellular processes
- Protease and Inhibitor Mechanisms
- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- dental development and anomalies
- RNA modifications and cancer
- NF-κB Signaling Pathways
- MicroRNA in disease regulation
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Osteoarthritis Treatment and Mechanisms
- DNA and Nucleic Acid Chemistry
University of Alabama at Birmingham
2015-2024
Ziauddin Hospital
2023
Comprehensive Blood & Cancer Center
2015
University of Vermont
2015
Institute for Molecular Medicine
2015
John Wiley & Sons (United States)
2015
University of California, Los Angeles
2015
Hudson Institute
2015
University of Alabama
2011-2014
National Medical Research Center of Dentistry and Maxillofacial Surgery
2011
Both activating and null mutations of proteins required for canonical WNT signaling have revealed the importance this pathway normal skeletal development. However, tissue-specific transcriptional mechanisms through which promotes differentiation bone-forming cells yet to be identified. Here, we address hypothesis that bone-related transcription factor RUNX2/CBFA1/AML3 are functionally linked components a onset osteoblast differentiation. Our findings show that, in bone SFRP1 (secreted...
Oxidative stress plays a critical role in the pathogenesis of atherosclerosis including formation lipid laden macrophages and development inflammation. However, oxidative stress-induced molecular signaling that regulates vascular calcification has not been investigated depth. Osteogenic differentiation smooth muscle cells (VSMC) is atherosclerotic lesions. An important contributor to lesions hydrogen peroxide from diverse sources cells. In this study we defined operative H2O2-induced VSMC...
Rationale: Vascular calcification is a hallmark of atherosclerosis, major cause morbidity and mortality in the United States. We have previously reported that osteogenic transcription factor Runx2 an essential sufficient regulator vascular smooth muscle cells (VSMC) vitro. Objective: To determine contribution differentiation VSMC to pathogenesis function VSMC-derived regulating vivo. Methods Results: SMC-specific Runx2-deficient mice, generated by breeding SM22α-Cre mice with exon 8 floxed...
The Runx2 (Cbfa1/AML3) transcription factor and matrix metalloproteinase 9 (MMP9) are key regulators of growth plate maturation bone formation. genes for both proteins characteristic markers breast prostate cancer cells that metastasize to bone. Here we experimentally addressed the compelling question whether MMP functionally linked. By cDNA expression array analysis, identified MMP9 as a novel downstream target Runx2. Like MMP13, is nearly depleted in mutant mice. Chromatin...
Genetic studies show that Msx2 and Dlx5 homeodomain (HD) proteins support skeletal development, but null mutation of the closely related Dlx3 gene results in early embryonic lethality. Here we find expression mouse embryo is associated with new bone formation regulation osteoblast differentiation. expressed osteoblasts, overexpression osteoprogenitor cells promotes, while specific knock-down by RNA interference inhibits, induction osteogenic markers. We characterized relation to during...
Runx (Cbfa/AML) transcription factors are critical for tissue-specific gene expression. A unique targeting signal in the C terminus directs to discrete foci within nucleus. Using Runx2/CBFA1/AML3 and its essential role osteogenesis as a model, we investigated fundamental importance of fidelity subnuclear localization tissue differentiating activity by deleting intranuclear via homologous recombination. Mice homozygous deletion (Runx2ΔC) do not form bone due maturational arrest osteoblasts....
The bone morphogenetic protein (BMP)-2 is a potent osteoinductive signal, inducing formation in vivo and osteoblast differentiation from non-osseous cells vitro. runt domain-related Cbfa1/PEBP2αA/AML-3 critical component of transcriptional regulator differentiation. To investigate the relationship between extracellular BMP-2 Cbfa1, osteogenesis, we examined expression Cbfa1 osteoblastic genes during induced osteogenic transdifferentiation myoblastic cell line C2C12. treatment completely...
CCAAT/enhancer-binding proteins (C/EBP) are critical determinants for cellular differentiation and cell type-specific gene expression. Their functional roles in osteoblast development have not been determined. We addressed a key component of the mechanisms by which C/EBP factors regulate transcription tissue-specific during differentiation. Expression both C/EBPbeta C/EBPdelta increases from growth to maturation developmental stages and, like bone-specific osteocalcin (OC) gene, is also...
ABSTRACT The Runt related transcription factors RUNX (AML/CBFα/PEBP2α) are key regulators of hematopoiesis and osteogenesis. Using co-transfection experiments with four natural promoters, including those the osteocalcin (OC), multi drug resistance (MDR), Rous Sarcoma Virus long terminal repeat (LTR), bone sialoprotein (BSP) genes, we show that each these promoters responds differently to forced expression proteins. However, three subtypes (i.e. AML1, AML2, AML3) regulate promoter in a...
Two regulatory pathways, bone morphogenetic protein (BMP)/transforming growth factor-β (TGFβ) and the transcription factor RUNX2, are required for formation in vivo. Here we show interdependent requirement of these pathways to induce an osteogenic program. A panel Runx2 deletion point mutants was used examine RUNX2-SMAD protein-protein interaction biological consequences on BMP2-induced signaling determined null cells. These cells do not respond BMP2 signal absence Runx2. We established that...
Several homeodomain (HD) proteins are critical for skeletal patterning and respond directly to BMP2 as an early step in bone formation. RUNX2, the earliest transcription factor proven essential commitment osteoblastogenesis, is also expressed response BMP2. However, there a gap our knowledge of regulatory cascade from signaling onset osteogenesis. Here we show that induces DLX3, protein activates Runx2 gene transcription. Small interfering RNA knockdown studies osteoblasts validate DLX3...
p300 is a multifunctional transcriptional coactivator that serves as an adapter for several transcription factors including nuclear steroid hormone receptors. possesses intrinsic histone acetyltransferase (HAT) activity may be critical promoting steroid-dependent activation. In osteoblastic cells, of the bone-specific osteocalcin (OC) gene principally regulated by Runx2/Cbfa1 factor and stimulated in response to vitamin D(3) via receptor complex. Therefore, we addressed control basal...
Abstract Cbfa1/Runx2 is a transcription factor essential for bone formation and osteoblast differentiation. Two major N-terminal isoforms of Cbfa1, designated type I/p56 (PEBP2aA1, starting with the sequence MRIPV) II/p57 (til-1, MASNS), each regulated by distinct promoters, are known. Here, we show that I transcript constitutively expressed in nonosseous mesenchymal tissues progenitor cells. Cbfa1 isoform expression does not change differentiation status In contrast, II increased during...
Runx transcription factors comprise a family of proteins that are essential for organogenesis. A unique nuclear matrix-targeting signal in the C terminus directs these to their appropriate subnuclear domains. At sites, they interact with coregulatory and target genes. We have previously shown aberrant expression Runx2 DNA binding domain metastatic breast cancer cells can prevent production osteolytic lesions bone. Here, we show proper targeting is required osteolysis. identified point...
During cell division, cessation of transcription is coupled with mitotic chromosome condensation. A fundamental biological question how gene expression patterns are retained during mitosis to ensure the phenotype progeny cells. We suggest that fate-determining factors provide an epigenetic mechanism for retention division. Runx proteins lineage-specific essential hematopoietic, neuronal, gastrointestinal, and osteogenic fates. Here we show Runx2 protein stable division remains associated...
Synthesis of cartilage by chondrocytes is an obligatory step for endochondral ossification. Global deletion the Runx2 gene results in complete failure ossification process, but underlying cellular and molecular mechanisms are not fully known. Here, we elucidated regulatory control distinctive to chondrocyte tissue generating exon 8 floxed mice. Deletion caused lethality at birth. The limbs Runx2(ΔE8/ΔE8) mice were devoid mature chondrocytes, vasculature, marrow. We demonstrate that...