Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Matrix”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,567 records · Page 87Linked to original sources
PubMed2003

Effects of matrix metalloproteinase inhibitors on bone resorption and orthodontic tooth movement.

Matrix metalloproteinases are involved in the regulation of bone remodeling. The hypothesis that matrix metalloproteinase inhibitors may be useful for experimentally limiting orthodontic tooth movement, a process involving perturbations of normal bone remodeling, was tested. General matrix metalloproteinase inhibitors limited the resorption of bone slices by mouse marrow cultures stimulated by calcitriol, parathyroid hormone, and basic-fibroblast growth factor. Pre-coating dentin slices with short arginine-glycine aspartic acid (RGD) peptides, but not arginine-glycine-glutamic acid (RGE) controls, restored bone resorption in the presence of matrix metalloproteinase inhibitors. Orthodontic tooth movement was inhibited by local delivery of Ilomastat, a general matrix metalloproteinase inhibitor, with the use of ethylene-vinyl-acetate (ELVAX) 40, a non-biodegradable, non-inflammatory sustained-release polymer. This study shows that orthodontic tooth movement can be inhibited with the use of matrix metalloproteinase inhibitors, and suggests a mechanistic link between matrix metalloproteinase activity and the production of RGD peptides.

Amides↗
PubMed1985

Gestational changes in the germinal matrix of the normal rhesus monkey fetus.

To explain the reported predisposition to germinal matrix hemorrhage in premature infants, pathogenetically important morphological features of the germinal matrix should be present in the 3rd trimester and rapidly change near term. Such features were sought in this study of the germinal matrix and its vasculature in normal rhesus monkey fetuses. The matrix cells, glia, ependyma, and capillaries showed no important structural changes during the 3rd trimester. The terminal vein tributaries were greatly enlarged by 148 days, but cellular and collagen support in their walls was minimal at this time. The latter features developed by the final days of gestation. These findings do not support a structural immaturity or specialization of the germinal matrix predisposing to germinal matrix hemorrhage. Our results, therefore, support the recent emphasis on physiological parameters in the pathogenesis and prevention of germinal matrix hemorrhage.

Animals↗
PubMed1994

Parathyroid-responsive modifications in the nuclear matrix of ROS 17/2.8 rat osteosarcoma cells.

PTH is a mediator of skeletal development and remodeling that influences gene expression in osteoblastic cells. It is well established that PTH modulates the activity of membrane-associated second messenger signal transduction pathways. In these studies we have addressed the potential contribution of components of cell structure to the integration of PTH-related regulatory signals that influence the expression of bone cell genes. Chronic treatment of ROS 17/2.8 rat osteosarcoma cells with PTH is accompanied by changes in gene expression that are at least in part transcriptionally controlled. To explore the involvement of nuclear architecture in PTH-responsive modifications in gene expression, we investigated changes in the nuclear matrix after PTH treatment. Consistent with a role for the nuclear matrix in determining spatial organization and topology of chromatin as well as in the localization and targeting of transcription factors, we observed PTH-associated changes in a 200-kilodalton nuclear matrix protein in response to PTH. A significant down-regulation of synthesis was observed when nuclear matrix proteins were resolved electrophoretically in two-dimensional gels. This protein was restricted to the nuclear matrix and was not detected in the chromatin or cytoskeletal cellular fractions. These alterations in nuclear matrix proteins that occur after PTH treatment in osteosarcoma cells were phenotype related. They did not occur in UMR-106 POL or H4 hepatoma cells. Our findings support a role for the nuclear matrix in transducing PTH-mediated regulatory signals to facilitate the extent to which genes in osteoblasts are transcribed.

Animals↗
PubMed2001

Matrix gamma-carboxyglutamic acid protein is a key regulator of PTH-mediated inhibition of mineralization in MC3T3-E1 osteoblast-like cells.

As part of its overall function as a major regulator of calcium homeostasis, PTH stimulates bone resorption and inhibits osteoblast-mediated biomineralization. To determine the basis for the inhibitory actions of this hormone, we compared the time course of PTH-dependent inhibition of mineralization in MC3T3-E1 osteoblast-like cells with changes in mRNA levels for several extracellular matrix proteins previously associated either with induction or inhibition of mineralization. Mineralizing activity was rapidly lost in PTH-treated cells ( approximately 30% inhibition after 3 h, 50% inhibition at 6 h). Of the proteins examined, changes in matrix gamma-carboxyglutamic acid protein were best correlated with PTH-dependent inhibition of mineralization. Matrix gamma-carboxyglutamic acid protein mRNA was rapidly induced 3 h after PTH treatment, with a 6- to 8-fold induction seen after 6 h. Local in vivo injection of PTH over the calvaria of mice also induced a 2-fold increase in matrix gamma-carboxyglutamic acid protein mRNA. Warfarin, an inhibitor of matrix gamma-carboxyglutamic acid protein gamma-carboxylation, reversed the effects of PTH on mineralization in MC3T3-E1 cells, whereas vitamin K enhanced PTH activity, as would be expected if a gamma-carboxyglutamic acid-containing protein were required for PTH activity. Levels of the other mRNAs examined were not well correlated with the observed changes in mineralization. Osteopontin, an in vitro inhibitor of mineralization, was induced approximately 4-fold 12 h after PTH addition. Bone sialoprotein mRNA, which encodes an extracellular matrix component most frequently associated with mineral induction, was inhibited by 50% after 12 h of PTH treatment. Osteocalcin mRNA, encoding the other known gamma-carboxyglutamic acid protein in bone, was also inhibited by PTH, but, again, with a significantly slower time course than was seen for mineral inhibition. Taken together, these results show that the rapid inhibition of osteoblast mineralization induced by in vitro PTH treatment is at least in part explained by induction of matrix gamma-carboxyglutamic acid protein.

1-Carboxyglutamic Acid↗
PubMed1990

Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns.

The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression.

Androgen-Binding Protein↗
PubMed1995

Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture.

This study focuses on the effect of static and dynamic mechanical compression on the biosynthetic activity of chondrocytes cultured within agarose gel. Chondrocyte/agarose disks (3 mm diameter) were placed between impermeable platens and subjected to uniaxial unconfined compression at various times in culture (2-43 days). [35S]sulfate and [3H]proline radiolabel incorporation were used as measures of proteoglycan and protein synthesis, respectively. Graded levels of static compression (up to 50%) produced little or no change in biosynthesis at very early times, but resulted in significant decreases in synthesis with increasing compression amplitude at later times in culture; the latter observation was qualitatively similar to that seen in intact cartilage explants. Dynamic compression of approximately 3% dynamic strain amplitude (approximately equal to 30 microns displacement amplitude) at 0.01-1.0 Hz, superimposed on a static offset compression, stimulated radiolabel incorporation by an amount that increased with time in culture prior to loading as more matrix was deposited around and near the cells. This stimulation was also similar to that observed in cartilage explants. The presence of greater matrix content at later times in culture also created differences in biosynthetic response at the center versus near the periphery of the 3 mm chondrocyte/agarose disks. The fact that chondrocyte response to static compression was significantly affected by the presence or absence of matrix, as were the physical properties of the disks, suggested that cell-matrix interactions (e.g. mechanical and/or receptor mediated) and extracellular physicochemical effects (increased [Na+], reduced pH) may be more important than matrix-independent cell deformation and transport limitations in determining the biosynthetic response to static compression. For dynamic compression, fluid flow, streaming potentials, and cell-matrix interactions appeared to be more significant as stimuli than the small increase in fluid pressure, altered molecular transport, and matrix-independent cell deformation. The qualitative similarity in the biosynthetic response to mechanical compression of chondrocytes cultured in agarose gel and chondrocytes in intact cartilage further indicates that gel culture preserves certain physiological features of chondrocyte behavior and can be used to investigate chondrocyte response to physical and chemical stimuli in a controlled manner.

Animals↗
PubMed1995

Cytoskeletal filament assembly and the control of cell spreading and function by extracellular matrix.

This study was undertaken to analyze how cell binding to extracellular matrix produces changes in cell shape. We focused on the initial process of cell spreading that follows cell attachment to matrix and, thus, cell 'shape' changes are defined here in terms of alterations in projected cell areas, as determined by computerized image analysis. Cell spreading kinetics and changes in microtubule and actin microfilament mass were simultaneously quantitated in hepatocytes plated on different extracellular matrix substrata. The initial rate of cell spreading was highly dependent on the matrix coating density and decreased from 740 microns 2/h to 50 microns 2/h as the coating density was lowered from 1000 to 1 ng/cm2. At approximately 4 to 6 hours after plating, this initial rapid spreading rate slowed and became independent of the matrix density regardless of whether laminin, fibronectin, type I collagen or type IV collagen was used for cell attachment. Analysis of F-actin mass revealed that cell adhesion to extracellular matrix resulted in a 20-fold increase in polymerized actin within 30 minutes after plating, before any significant change in cell shape was observed. This was followed by a phase of actin microfilament disassembly which correlated with the most rapid phase of cell extension and ended at about 6 hours; F-actin mass remained relatively constant during the slow matrix-independent spreading phase. Microtubule mass increased more slowly in spreading cells, peaking at 4 hours, the time at which the transition between rapid and slow spreading rates was observed. However, inhibition of this early rise in microtubule mass using either nocodazole or cycloheximide did not prevent this transition. Use of cytochalasin D revealed that microfilament integrity was absolutely required for hepatocyte spreading whereas interference with microtubule assembly (using nocodazole or taxol) or protein synthesis (using cycloheximide) only partially suppressed cell extension. In contrast, cell spreading could be completely inhibited by combining suboptimal doses of cytochalasin D and nocodazole, suggesting that intact microtubules can stabilize cell form when the microfilament lattice is partially compromised. The physiological relevance of the cytoskeleton and cell shape in hepatocyte physiology was highlighted by the finding that a short exposure (6 hour) of cells to nocodazole resulted in production of smaller cells 42 hours later that exhibited enhanced production of a liver-specific product (albumin). These data demonstrate that spreading and flattening of the entire cell body is not driven directly by net polymerization of either microfilaments or microtubules.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

Cell-surface transglutaminase promotes fibronectin assembly via interaction with the gelatin-binding domain of fibronectin: a role in TGFbeta-dependent matrix deposition.

Assembly of fibronectin into a fibrillar matrix is critical for regulation of cell growth and migration, embryogenesis and wound healing. We have previously shown that cell-surface tissue transglutaminase serves as an integrin-binding adhesion coreceptor for fibronectin. Here we report that transglutaminase strongly promotes fibronectin assembly mediated by alpha5beta1 integrin. This effect is independent from transglutaminase-mediated enzymatic crosslinking of fibronectin and separate from the ability of transglutaminase to stimulate cell spreading. Surface transglutaminase increases the binding of fibronectin to cells via interaction with its gelatin-binding domain that contains modules I6II1,2I7-9 and lacks integrin-binding motifs. The gelatin-binding fragment of fibronectin binds to surface transglutaminase on cells in suspension but does not interact with cell monolayers where surface transglutaminase is occupied by fibronectin. Surface transglutaminase colocalizes with growing fibronectin fibrils at early timepoints of matrix formation and remains codistributed with fibronectin matrices thereafter. The observed stimulation of matrix assembly by transglutaminase is blocked by the gelatin-binding fragment of fibronectin, but is not strongly perturbed by its N-terminal fragment consisting of modules I1-5. These results implicate an interaction between transglutaminase and the gelatin-binding domain of fibronectin in matrix assembly and suggest its role in initiation of fibrillogenesis. However, blocking antibodies against alpha5beta1 integrin or the cell-binding fragment of fibronectin that contains modules III2-11 most strongly suppress matrix formation and abolish the effects of transglutaminase. Hence, transglutaminase cooperates with but can not substitute for alpha5beta1 integrin in fibronectin assembly. Treatment of fibroblasts with transforming growth factor beta (TGFbeta) significantly increases surface expression of transglutaminase and its association with beta1 integrins, but not with alphaVbeta3 integrin. TGFbeta enhances the binding of fibronectin to the cell surface and elevates matrix formation, whereas antibody against transglutaminase or the gelatin-binding fragment of fibronectin suppresses these effects, indicating an involvement of transglutaminase in TGFbeta-dependent fibronectin assembly. Therefore, TGFbeta-induced fibronectin matrix deposition during normal wound healing or fibrotic disorders may depend on upregulation of integrin-associated surface transglutaminase.

Animals↗
PubMed1985

Extracellular matrix interactions with the apical surface of vascular endothelial cells.

Cultured aortic endothelial cells, like their in vivo counterparts, form highly organized, confluent monolayers of polarized epithelioid cells that secrete, exclusively at their basal surface, an extracellular matrix to which they then attach. The influence of isolated subendothelial matrix preparations on cell polarity and monolayer organization was studied by presenting fragments of the matrix to confluent bovine aortic endothelial cell cultures. The matrix particles were immediately bound to the apical aspect of the cell monolayer and induced rapid reorganization of the monolayer into cells with a fibroblastoid morphology. To determine if fibronectin, the major glycoprotein of the subendothelial matrix, could be involved in the observed apical cell surface-matrix interactions, latex beads or small discs of Nucleopore filters were coated with the glycoprotein and presented to confluent monolayers. In a fashion similar to that observed with matrix fragments, materials coated with fibronectin caused focal reorganization of the cell layer. After contact with the coated beads, the underlying endothelial cells flowed upward and spread over the entire bead, forming a canopy of confluent cells that draped the particle. Contact of confluent monolayers with the coated filters induced similar behaviour, except that monolayer reorganization into the fibroblastoid phenotype was followed by emigration of the majority of underlying cells through the pores to the upper filter surface, where they formed a new organized cell monolayer with the typical endothelial cell morphology. Thus contact of the apical surface of endothelial cells with structures to which they adhere initiates a rapid disruption of the organized cell monolayer, followed immediately by a concerted effort of the local population to re-establish both cell polarity and monolayer contiguity. The expression of this behaviour may be important during tissue remodeling that occurs in neovascularization and during interactions with thromboemboli.

Animals↗
PubMed2005

Enamel matrix protein interactions.

UNLABELLED: The recognized structural proteins of the enamel matrix are amelogenin, ameloblastin, and enamelin. While a large volume of data exists showing that amelogenin self-assembles into multimeric units referred to as nanospheres, other reports of enamel matrix protein-protein interactions are scant. We believe that each of these enamel matrix proteins must interact with other organic components of ameloblasts and the enamel matrix. Likely protein partners would include integral membrane proteins and additional secreted proteins. INTRODUCTION: The purpose of this study was to identify and catalog additional proteins that play a significant role in enamel formation. MATERIALS AND METHODS: We used the yeast two-hybrid assay to identify protein partners for amelogenin, ameloblastin, and enamelin. Once identified, RT-PCR was used to assess gene transcription of these newly identified and potential "enamel" proteins in ameloblast-like LS8 cells. RESULTS: In the context of this yeast assay, we identified a number of secreted proteins and integral membrane proteins that interact with amelogenin, ameloblastin, and enamelin. Additionally, proteins whose functions range from the inhibition of soft tissue mineralization, calcium ion transport, and phosphorylation events have been identified as protein partners to these enamel matrix proteins. For each protein identified using this screening strategy, future studies are planned to confirm this physiological relationship to biomineralization in vivo. CONCLUSION: Identifying integral membrane proteins of the secretory surface of ameloblast cells (Tomes' processes) and additional enamel matrix proteins, based on their abilities to interact with the most abundant enamel matrix proteins, will better define the molecular mechanisms of enamel formation at its most rudimentary level.

Ameloblasts↗
PubMed2005

Developmental regulation and coordinate reexpression of FKBP65 with extracellular matrix proteins after lung injury suggest a specialized function for this endoplasmic reticulum immunophilin.

AFKBP65 (65-kDa FK506-binding protein) is an endoplasmic reticulum (ER)-localized peptidyl-prolyl cis-trans isomerase predicted to play a role in the folding and trafficking of secretory proteins. In previous studies, we have shown that FKBP65 is developmentally regulated and associates with the extracellular matrix protein, tropoelastin, during its maturation and transport through the ER. In this study, we show that FKBP65 is expressed in the lung with the same developmental pattern as tropoelastin and other matrix proteins. To test the hypothesis that FKBP65 is upregulated at times when extracellular matrix proteins are being actively synthesized and assembled, adult mice were treated with bleomycin to cause reinitiation of matrix protein production during the ensuing development of pulmonary fibrosis. After bleomycin instillation, FKBP65 expression was reactivated in the lung with a pattern similar to that observed for tropoelastin and type I collagen. Using human lung fibroblast cultures, we showed that FKBP65 does not undergo the unfolded protein response, a response associated with an upregulation of resident ER proteins that occurs after increased ER stress. When fibroblasts were treated with transforming growth factor (TGF)-beta1, which is upregulated during the development of pulmonary fibrosis and known to induce matrix production, FKBP65 expression and synthesis was also increased. Similar to type I collagen and tropoelastin, this response was completely inhibited in a dose-dependent manner by GGTI-298, a geranylgeranyl transferase I inhibitor. Treatment of fibroblasts with an inhibitor of ribonucleic acid (RNA) polymerase II after TGF-beta1 treatment showed that the effect of TGF-beta1 was not because of increased stabilization of the FKBP65 messenger RNA. In summary, we have shown that FKBP65 is highly expressed in lung development, downregulated in the adult, and can be reactivated in a coordinated manner with extracellular matrix proteins after lung injury. The expression pattern of FKBP65, which is atypical for general ER foldases, suggests that FKBP65 has a distinct set of developmentally regulated protein ligands. The response to injury, which may be in part a direct response to TGF-beta1, assures the presence of FKBP65 in the ER of cells actively producing components of the extracellular matrix.

Animals↗
PubMed2006

Microrheology and ROCK signaling of human endothelial cells embedded in a 3D matrix.

Cell function is profoundly affected by the geometry of the extracellular environment confining the cell. Whether and how cells plated on a two-dimensional matrix or embedded in a three-dimensional (3D) matrix mechanically sense the dimensionality of their environment is mostly unknown, partly because individual cells in an extended matrix are inaccessible to conventional cell-mechanics probes. Here we develop a functional assay based on multiple particle tracking microrheology coupled with ballistic injection of nanoparticles to measure the local intracellular micromechanical properties of individual cells embedded inside a matrix. With our novel assay, we probe the mechanical properties of the cytoplasm of individual human umbilical vein endothelial cells (HUVECs) embedded in a 3D peptide hydrogel in the presence or absence of vascular endothelial growth factor (VEGF). We found that VEGF treatment, which enhances endothelial migration, increases the compliance and reduces the elasticity of the cytoplasm of HUVECs in a matrix. This VEGF-induced softening response of the cytoplasm is abrogated by specific Rho-kinase (ROCK) inhibition. These results establish combined particle-tracking microrheology and ballistic injection as the first method able to probe the micromechanical properties and mechanical response to agonists and/or drug treatments of individual cells inside a matrix. These results suggest that ROCK plays an essential role in the regulation of the intracellular mechanical response to VEGF of endothelial cells in a 3D matrix.

Cell Culture Techniques↗
PubMed1996

Effect of cross-linking on matrix permeability. A model for AGE-modified basement membranes.

There is much evidence that basement membranes, such as in the renal glomerulus, act as macromolecular sieves, restricting the passage of proteins. Cross-linking of matrix proteins, as occurs because of advanced glycosylation end products (AGEs) in diabetes, may have an effect on the sieving properties of the basement membrane. To test this hypothesis, Matrigel, a basement membrane-like matrix, was cross-linked with glycolaldehyde and control and cross-linked matrices compared. Control matrices allowed less bovine serum albumin to pass through than did cross-linked matrices, with sieving coefficients (SCs) of 0.38 +/- 0.02 and 0.52 +/- 0.02, respectively (P < 0.0005). The control matrices also allowed less cross-linked albumin through than did the cross-linked matrices: 0.13 +/- 0.01 vs. 0.17 +/- 0.02 (P < 0.002). The SCs of a series of fluorescein isothiocyanate dextrans (four sizes, Mr 16,000- 168,000) were lower for the control matrix than for the cross-linked matrix (P < 0.03). In addition, the SC for glycated albumin (incubated with glucose-6-phosphate) was higher than that of normal albumin for both the control (P < 0.04) and cross-linked matrices (P < 0.001). These data indicate that cross-linking of the matrix increases permeability to macromolecules. Analysis of the data using fiber-matrix theory suggests that the mean fiber radius was increased in the cross-linked matrix. The data also indicate that glycated albumin filters through the matrices more easily than does normal albumin. In relation to the situation seen in vivo, it is possible that glycation of circulating proteins and AGE modification of glomerular basement membrane proteins may both contribute to the proteinuria seen in diabetes.

Basement Membrane↗
PubMed1989

Bone induction by fetal and adult human bone matrix in athymic rats.

In the rat the intramuscular implantation of demineralized rat bone matrix induces local bone formation. In adult primates, however, allogenous bone matrix induces little or no bone formation in extraskeletal sites. To assay inductive properties, human demineralized bone matrix from 6 adult donors and 4 fetuses was implanted intramuscularly in athymic rats for 6 weeks. Fetal and adult matrix implants yielded about the same amount of bone: about half of the bone yield from rat or rabbit matrix in the same model. We conclude that human bone matrix has inductive properties and that failures to induce bone formation in adult primates may be due to an inability by the recipients to respond to inductive stimuli of adult bone matrix.

Adolescent↗
PubMed1998

A study on the relationship between antisense EGFR cDNA fragments and nuclear matrix proteins in glioblastoma cells.

The association of antisense epidermal growth factor receptor (EGFR) cDNA fragments with nuclear matrix from EGFR-antisense transfected glioblastoma cell lines U343 and U87 was investigated. A 1015 bp DNA fragment (primer I-II) was amplified in both genomic DNA and nuclear matrix-associated DNA (NM DNA) from EGFR-antisense transfected glioblastoma cell lines U343E and U87E. Two different DNA fragments (940 bp and 110 bp) were amplified by primer I-III in both genomic DNA and NM DNA of U343E, while one 110 bp PCR product was shown with the same primer in both genomic DNA and NM DNA of U87E only. After EGFR-antisense transfection, the binding property of the 110 bp DNA fragment (primer IV-V) to nuclear matrix was not affected. Southwestern blotting demonstrated the presence of antisense EGFR cDNA binding nuclear matrix proteins. Our findings demonstrate that not only EGFR DNA is associated with nuclear matrix, but the transfected antisense EGFR cDNA also binds to nuclear matrix proteins. The nuclear matrix is most likely involved in the replication and transcription of antisense EGFR cDNA or hybridisation with sense mRNA in vitro.

Brain Neoplasms↗
PubMed2000

Nuclear matrix targeting of steroid receptors: specific signal sequences and acceptor proteins.

The nuclear matrix provides the framework for various processes that occur within the nucleus such as transcription, replication, and splicing. As the composition of the nuclear matrix varies between different cell types, the matrix may influence cell-type-specific gene expression. A number of transcription factors have been shown to be associated with the nuclear matrix, including steroid hormone receptors that were the first transcriptional regulatory proteins localized to this compartment. In this review we highlight the most recent advances in our understanding of steroid hormone receptor targeting to the matrix. A specific nuclear matrix targeting signal (NMTS) has been identified within the glucocorticoid receptor (GR) that includes portions of its DNA-binding domain and tau2 transactivation domains. Distinct nuclear matrix acceptor proteins appear to interact within the GR NMTS and impart divergent effects on the transcriptional regulatory properties of the receptor.

Amino Acid Motifs↗
PubMed2000

NP/NMP4 transcription factors have distinct osteoblast nuclear matrix subdomains.

The mechanisms underlying the coupling of type I collagen and matrix metalloproteinase (MMP) expression to cell structure and adhesion are poorly understood. We propose that nuclear matrix architectural transcription factors link cell structure and transcription via their association with nuclear matrix subdomains and by their capacity for altering promoter geometry. NP/NMP4 are nuclear matrix proteins that contain from five to eight Cys(2)His(2) zinc fingers. Some NP/NMP4 isoforms bind to the rat type I collagen alpha1(I) polypeptide chain promoter in the manner of architectural transcription factors and alter basal transcription in osteoblast-like cells (Thunyakitpisal et al. in review). Certain isoforms of NP/NMP4 are identical to CIZ, Cas-interacting zinc finger protein, a nucleocytoplasmic shuttling protein that associates with focal adhesions and regulates MMP expression [Nakamoto et al. (2000): Mol Cell Biol 20:1649-1658]. To better understand the role of subnuclear architecture in collagen and MMP expression, we mapped the osteoblast nuclear distribution of NP/NMP4 proteins and identified the functional motifs necessary for nuclear localization and nuclear matrix targeting. Immunofluorescence microscopy was used to determine the cellular and subnuclear distribution of native NP/NMP4 proteins and green fluorescent protein (GFP)-NP/NMP4 fusion proteins in osteoblast-like cells. All GFP-NP/NMP4 fusion proteins localized to the nucleus, but accumulated in distinct nuclear matrix subdomains. The zinc finger domain was necessary and sufficient for nuclear import and matrix targeting. We conclude that the arrangement of the NP/NMP4 zinc fingers largely determines the subnuclear location of these isoforms.

Amino Acid Motifs↗
PubMed2000

Ultrastructural, cytochemical, and biophysical aspects of mechanisms of bone matrix calcification.

Primary calcification in embryonic ossification occurs as follows: crystallization within matrix vesicles, formation of calcified nodules, and finally the establishment of expansive calcified matrix. However, the participation of the matrix vesicles in other types of bone calcification, such as bone formation during bone remodeling in adults has not been examined sufficiently. We introduce our recent observations on the presence of matrix vesicles in aged bones. In addition, although it is well known that the extracellular fluid supersaturates the calcification crystal, hydroxyapatite, the specific mechanisms by which bone matrix calcify remain unclear. In order to further approach the mechanisms of bone matrix calcification, we also review ultrastructural and localizational alterations of the matrix organics according to the progression of calcification, and an evaluation of mineral micro-environment in the calcifying sites by energy-filter transmission electron microscopy.

Animals↗