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At least 1,495 records · Page 83Linked to original sources
PubMed2004

Primary culture of rat growth plate chondrocytes: an in vitro model of growth plate histotype, matrix vesicle biogenesis and mineralization.

During endochondral ossification (EO), cartilage is replaced by bone. Chondrocytes of growth plate undergo proliferation, maturation, hypertrophy, matrix vesicle (MV) biogenesis and programmed cell death (PCD, apoptosis). The in vitro system presented here provides a potential experimental model for studying in vitro differentiation and MV biogenesis in chondrocyte cultures. Chondrocytes were obtained from collagenase-digested tibial and femoral growth plate cartilage of 7-week-old rachitic rats. The isolated chondrocytes were plated as monolayers at a density of 0.5 x 10(6) cells per 35-mm plate and grown for 17 days in BGJ(b) medium supplemented with 10% fetal bovine serum, 50 microg/ml ascorbic acid. Light microscopy revealed Sirius red-positive, apparent bone matrix in layers at the surfaces of cartilaginous nodules that developed in the cultures. The central matrix was largely alcian blue staining thus resembling cartilage matrix. Electron microscopy revealed superficial areas of bone like matrix with large banded collagen fibrils, consistent with type I collagen. Most of the central matrix was cartilaginous, with small fibrils, randomly arranged consistent with type II collagen. The presence of peripheral type I and central type II and type X collagen was confirmed by immunohistochemical staining. Immunohistochemistry with anti-Bone morphogenetic proteins 2, 4 and 6 showed that BMP expression is associated with maturing hypertrophic central chondrocytes, many of which were TUNEL positive and undergoing cell death with plasma membrane breaks, hydropic swelling and cell fragmentation. During early mineralization, small radial clusters of hydroxyapatite-like mineral were associated with matrix vesicles. Collagenase digestion-released MVs from the cultures showed a high specific activity for alkaline phosphatase and demonstrated a pattern of AMP-stimulated nonradioactive (40)Calcium deposition comparable to that observed with native MVs. These studies confirm that primary cultures of rat growth plate chondrocytes are a reasonable in vitro model of growth plate histotype, MV biogenesis and programmed cell death.

Alkaline Phosphatase↗
PubMed2006

Periostin promotes atrioventricular mesenchyme matrix invasion and remodeling mediated by integrin signaling through Rho/PI 3-kinase.

Recent evidence suggests that extracellular matrix components may play a signaling role in embryonic valve development. We have previously identified the spatiotemporal expression patterns of periostin in developing valves, but its function during this process is largely unknown. To evaluate the functional role periostin plays during valvulogenesis, two separate three-dimensional culture assay systems, which model chick atrioventricular cushion development, were employed. These assays demonstrated that cushion mesenchymal cells adhered and spread on purified periostin in a dose-responsive manner, similar to collagen I and fibronectin via alpha(v)beta(3) and beta(1) integrin pairs. Periostin overexpression resulted in enhanced mesenchyme invasion through 3D collagen gels and increased matrix compaction. This invasion was dependent on alpha(v)beta(3) more than beta(1) integrin signaling, and was mediated differentially by Rho kinase and PI 3-kinase. Both matrix invasion and compaction were associated with a colocalization of periostin and beta(1) integrin expression to migratory cell phenotype in both surface and deep cells. The Rho/PI 3-kinase pathway also differentially mediated matrix compaction. Both Rho and PI 3-kinase were involved in normal cushion mesenchyme matrix compaction, but only PI 3-kinase was required for the enhanced matrix compaction due to periostin. Taken together, these results highlight periostin as a mediator of matrix remodeling by cushion mesenchyme towards a mature valve structure.

Adenoviridae↗
PubMed2003

Positional mapping of specific DNA sequences relative to the nuclear substructure by direct polymerase chain reaction on nuclear matrix-bound templates.

Nuclear DNA of higher eukaryotes is organized in supercoiled loops anchored to a proteinaceous substructure commonly known as the nuclear matrix. Current evidence suggests that important processes of nuclear physiology, such as replication, transcription, and processing of primary transcripts, take place at macromolecular complexes located at discrete, well-defined sites upon the nuclear matrix. A number of authors have reported that actively transcribed genes are closely associated with the nuclear matrix. The topological relationship between the gene sequences located in the DNA loops and the nuclear matrix appears to be very important for appropriate nuclear physiology. Here, we describe a polymerase chain reaction-based method for directly mapping any DNA sequence position relative to the nuclear matrix that avoids the problem posed by DNA fragments nonspecifically bound to the nuclear matrix, without the need of purifying the specifically nuclear matrix-bound DNA.

Actins↗
PubMed2003

Modulation of cultured corneal keratocyte phenotype by growth factors/cytokines control in vitro contractility and extracellular matrix contraction.

The purpose of this study was to evaluate specific keratocyte phenotypes (keratocyte, fibroblast, myofibroblast) for cell contractility and ability to contract extracellular matrix. Rabbit keratocyte phenotype was modulated by exposure to optimal proliferative doses of IGF-I, IL-1alpha, FGF2, PDGF-AB, and TGFbeta(1). Cells were then evaluated by immunocytochemistry, western blot, collagen gel contraction and LPA stimulation to measure: (1) focal adhesion (FA), fibronectin (FN) and f-actin assembly; (2) expression of alpha-smooth muscle actin (alpha-SMA); (3) ability to contract extracellular matrix and (4) determine contractile ability, respectively. Untreated keratocytes showed no ability to contract collagen matrix. IGF-I and IL-1alpha increased cell proliferation (70.2 and 74.3%, respectively) but did not alter keratocyte phenotype or ability to contract matrix. FGF2 and PDGF induced fibroblast differentiation with FA and FN assembly and significant (p<0.05) extracellular matrix contraction. TGFbeta(1) induced myofibroblast differentiation with prominent FA and FN assembly, expression of alpha-SMA and significantly greater (p<0.05) matrix contraction. Addition of LPA induced actin filament assembly in growth factor starved fibroblasts and myofibroblasts but had no effect on the cultured keratocyte phenotype. We report for the first time that the keratocyte phenotype is non-contractile and that cell quiescence is not a defining characteristic. We further establish that changes in environmental conditions modulate the keratocyte phenotype resulting in physiologically functional differences regarding cell contractility and capacity to contract extracellular matrix.

Animals↗
PubMed2002

Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activator.

Investigations determined that the cell matrix-associated prekallikrein (PK) activator is prolylcarboxypeptidase. PK activation on human umbilical vein endothelial cell (HUVEC) matrix is inhibited by antipain (IC(50)=50 microM) but not anti-factor XIIa antibody, 3 mM benzamidine, 5 mM iodoacetic acid or iodoacetamide, or 3 mM N-ethylmaleimide. Corn trypsin inhibitor (IC(50)=100 nM) or Fmoc-aminoacylpyrrolidine-2-nitrile (IC(50)=100 microM) blocks matrix-associated PK activation. Angiotensin II (IC(50)=100 microM) or bradykinin (IC(50)=3 mM), but not angiotensin 1-7 or bradykinin 1-5, inhibits matrix-associated PK activation. ECV304 cell matrix PK activator also is blocked by 100 microM angiotensin II, 1 microM corn trypsin inhibitor, and 50 microM antipain, but not angiotensin 1-7. 1 mM angiotensin II or 300 microM Fmoc-aminoacylpyrrolidine-2-nitrile indirectly blocks plasminogen activation by inhibiting kallikrein formation for single chain urokinase activation. On immunoblot, prolylcarboxypeptidase antigen is associated with HUVEC matrix. These studies indicate that prolylcarboxypeptidase is the matrix PK activator.

Angiotensin II↗
PubMed1997

Extracellular matrix composition and gene expression in collagenous colitis.

BACKGROUND & AIMS: Collagenous colitis is a rare diarrheal disease of unknown pathophysiology that is histologically defined by subepithelial bandlike structures. The objective of this study was to elucidate the biochemical composition and the origin of the bandlike structures in collagenous colitis. METHODS: Immunohistochemical and in situ hybridization analyses were performed on endoscopic specimens using specific antibodies and riboprobes for collagen types I, III, IV, and VI and for the glycoprotein tenascin. RESULTS: In collagenous colitis, the mucosal matrix with the exception of the bands retained a normal architecture and extracellular matrix composition. The bands stained most prominently for type VI collagen and tenascin. Less abundant staining for both proteins was also found in the subepithelial matrix of the normal mucosa. In situ hybridization showed no significant increase in collagen type VI messenger RNA expression in cells around and entrapped in the bands in collagenous colitis compared with normal specimens. CONCLUSIONS: The results support the suggestion that collagenous colitis is a localized alteration of the extracellular matrix, which involves the pericryptal-subepithelial myofibroblast sheath. The data suggest that reduced matrix degradation and not overactivation of matrix synthesis may be the reason for the subepithelial accumulation of matrix proteins.

Adult↗
PubMed1995

The nuclear matrix as a site of anticancer drug action.

Many nuclear functions, including the organization of the chromatin within the nucleus, depend upon the presence of a nuclear matrix. Nuclear matrix proteins are involved in the formation of chromatin loops, control of DNA supercoiling, and regulation and coordination of transcriptional and replicational activities within individual loops. Various structural and functional components of the nuclear matrix represent potential targets for anticancer agents. Alkylating agents and ionizing radiation interact preferentially with nuclear matrix proteins and matrix-associated DNA. Other chemotherapeutic agents, such as fludarabine phosphate and topoisomerase II-active drugs, interact specifically with matrix-associated enzymes, such as DNA primase and the DNA topoisomerase II alpha isozyme. The interactions of these agents at the level of the nuclear matrix may compromise multiple nuclear functions and be relevant to their antitumor activities.

Animals↗
PubMed1992

Further considerations on the thermal stabilization of the nuclear matrix in mouse erythroleukemia cells.

The morphology and the polypeptide composition of the nuclear matrix obtained from 37 degrees C incubated nuclei has been studied in mouse erythroleukemia cells. From a structural point of view, in the absence of heat treatment, the matrix lacked identifiable nucleolar remnants and the internal fibrogranular meshwork whereas a peripheral lamina was seen. On the contrary, the matrix obtained from heat exposed nuclei displayed very electrondense nucleolar remnants and an abundant inner network. These results were obtained irrespective of the type of extracting agent (2M NaCl or 0.2 M (NH4)2SO4) used to remove histones and other soluble proteins. The heat stabilization of the matrix could not be prevented by sulfhydryl blocking chemicals such as iodoacetamide and n-ethylmaleimide, thus suggesting that heat does not stabilize the matrix by inducing the formation of disulfide bonds. Only limited differences in the polypeptide pattern of matrix isolated under different conditions were seen using one-dimensional pore gradient polyacrylamide gels stained with both Coomassie Brilliant Blue and silver despite the fact that the matrix fraction from heat treated nuclei retained about three fold more protein in comparison with controls. The same results were obtained also by means of two-dimensional non-equilibrium gel electrophoresis.

Ammonium Sulfate↗
PubMed2000

Fibronectin matrix composition and organization can regulate cell migration during amphibian development.

Fibronectin (FN) is an adhesive extracellular matrix component that is essential for vertebrate development. It forms a fibrillar matrix at the cell surface which controls cell morphology, migration, proliferation, and other important cellular processes. To address specific functions of FN matrix structure during early vertebrate development, we introduced normal and mutant recombinant FNs (recFNs) into the blastocoel cavity of embryos of the amphibian Pleurodeles waltl. Here we show that a native recFN FN(A-B-) as well as recFNs with specific mutations in the cell-binding domain, FN(RGD-) and FN(syn-), or in a FN-binding region, FNDeltaIII(1), are assembled into fibrillar matrix. A recFN (FNDeltaIII(1-7)) that forms a structurally distinct matrix in cultured cells was assembled into aggregates at the cell periphery and was able to inhibit assembly of endogenous amphibian FN matrix in a dose-dependent manner. Cell adhesion, spreading, and migration were perturbed in vitro and in vivo on chimeric matrices containing FN(RGD-), FN(syn-), or FNDeltaIII(1-7) co-assembled with amphibian FN. Developmentally, this perturbation resulted in defects in mesoderm patterning and inhibition of gastrulation. These results indicate that FN matrix fibrillar structure and composition are important determinants of cell adhesion and migration during development.

Amino Acid Motifs↗
PubMed1991

Indirect angiogenic agents do not release fibroblast growth factors from extracellular matrix.

Vascular growth factors are categorized as either primary or secondary angiogenic factors. Primary angiogenic agents such as fibroblast growth factors, not only induce the complete angiogenic response, but also stimulate the individual components of vascular growth. Secondary angiogenic agents can induce vascular growth, but they do not act through the direct stimulation of endothelial proliferation, migration, and protease production. Since fibroblast growth factors are known to bind to components of the extracellular matrix, we assessed whether secondary agents act through liberating growth factors from matrix storage sites. The study utilized L6 skeletal myoblasts in culture, which we demonstrated were capable of synthesizing extracellular matrix containing heparin binding endothelial mitogens. The heparin-binding mitogenic activity accumulated in a time-dependent fashion, and matrix extracts contained a protein with immunologic identity to acidic fibroblast growth factor. The ability of secondary angiogenic agents and related compounds including adenosine, inosine, hypoxanthine, nicotinamide, lactic acid, phorbol esters, prostaglandin E2, and copper (at concentrations of 1 microM and 1 mM) to release heparin binding mitogenic activity from the matrix was evaluated. The results demonstrate that although heparin is capable of releasing heparin-binding growth factors from extracellular matrix storage sites in a dose dependent fashion, none of the known secondary angiogenesis factors are capable of functioning in a similar fashion. Thus these secondary angiogenic factors do not appear to exert their effect through increasing the bioavailability of preformed heparin-binding growth factors sequestered in the extracellular matrix. The mechanism(s) whereby these agents induce vascular growth remains to be elucidated.

Animals↗
PubMed2001

Collagen VI deficiency affects the organization of fibronectin in the extracellular matrix of cultured fibroblasts.

Fibronectin is one of the main components of the extracellular matrix and associates with a variety of other matrix molecules including collagens. We demonstrate that the absence of secreted type VI collagen in cultured primary fibroblasts affects the arrangement of fibronectin in the extracellular matrix. We observed a fine network of collagen VI filaments and fibronectin fibrils in the extracellular matrix of normal murine and human fibroblasts. The two microfibrillar systems did not colocalize, but were interconnected at some discrete sites which could be revealed by immunoelectron microscopy. Direct interaction between collagen VI and fibronectin was also demonstrated by far western assay. When primary fibroblasts from Col6a1 null mutant mice were cultured, collagen VI was not detected in the extracellular matrix and a different pattern of fibronectin organization was observed, with fibrils running parallel to the long axis of the cells. Similarly, an abnormal fibronectin deposition was observed in fibroblasts from a patient affected by Bethlem myopathy, where collagen VI secretion was drastically reduced. The same pattern was also observed in normal fibroblasts after in vivo perturbation of collagen VI-fibronectin interaction with the 3C4 anti-collagen VI monoclonal antibody. Competition experiments with soluble peptides indicated that the organization of fibronectin in the extracellular matrix was impaired by added soluble collagen VI, but not by its triple helical (pepsin-resistant) fragments. These results indicate that collagen VI mediates the three-dimensional organization of fibronectin in the extracellular matrix of cultured fibroblasts.

Animals↗
PubMed2003

Characterization of an Mg2+-dependent endonucleolytic activity of the rat hepatocyte nuclear matrix.

Initial degradation of chromatin into high-molecular mass DNA fragments during apoptosis reflects the periodicity of chromatin organization into nuclear matrix-attached loops. In this article, we put forward the hypothesis that this pattern of DNA cleavage is also a result of the localization of an endonuclease on the nuclear matrix. Namely, we observed an endonucleolytic activity of the isolated rat hepatocyte nuclear matrix. It was Mg2+-dependent, with an optimal activity at pH 7.2 in the absence of either Na+ or K+. It was fully active in the presence of Zn2+ and capable of introducing single-strand breaks into plasmid DNA. It did not display a sequence-specific activity. A 23 kDa DNA nuclease that was principally localized on the rat hepatocyte nuclear matrix was detected. The enzyme shared the biochemical requirements with the nuclear matrix endonucleolytic activity, thus we proposed that p23 could be responsible for the endonucleolytic activity of the nuclear matrix. In view of its properties and preferential localization on the nuclear matrix, the endonuclease described herein could be a possible candidate that brings about initial DNA cleavage during apoptosis.

Animals↗
PubMed2006

Automated acoustic matrix deposition for MALDI sample preparation.

Novel high-throughput sample preparation strategies for MALDI imaging mass spectrometry (IMS) and profiling are presented. An acoustic reagent multispotter was developed to provide improved reproducibility for depositing matrix onto a sample surface, for example, such as a tissue section. The unique design of the acoustic droplet ejector and its optimization for depositing matrix solution are discussed. Since it does not contain a capillary or nozzle for fluid ejection, issues with clogging of these orifices are avoided. Automated matrix deposition provides better control of conditions affecting protein extraction and matrix crystallization with the ability to deposit matrix accurately onto small surface features. For tissue sections, matrix spots of 180-200 microm in diameter were obtained and a procedure is described for generating coordinate files readable by a mass spectrometer to permit automated profile acquisition. Mass spectral quality and reproducibility was found to be better than that obtained with manual pipet spotting. The instrument can also deposit matrix spots in a dense array pattern so that, after analysis in a mass spectrometer, two-dimensional ion images may be constructed. Example ion images from a mouse brain are presented.

Animals↗
PubMed1990

A nuclear matrix protein binds very tightly to DNA in the avian beta-globin gene enhancer.

Current evidence suggests that DNA is covalently attached to proteins in the nuclear matrix of eukaryotic cells and that specific DNA sequences are tightly associated with the nuclear matrix. However, it has not been documented that specific DNA sequences can become covalently attached to nuclear matrix protein. We have examined the binding of cloned DNA sequences that contain the avian beta-globin gene enhancer, a region previously shown to be matrix associated in erythroid cells in vivo, with nuclear matrices from several avian tissue sources to determine if covalent DNA-protein bonds are formed. Our results indicate that sequence-specific DNA-protein complexes that are resistant to denaturation by SDS, boiling, and phenol and disulfide reduction are formed. Excess protein, capable of forming very tight bonds with DNA that contains the beta-globin gene enhancer, is present in cells in which matrix attachment of this DNA sequence is not detected in vivo. Evidence is presented that suggests that the protein to which DNA forms very tight bonds is not topoisomerase II. These results are discussed in relation to current models of the nuclear matrix and the utility of in vitro assays of matrix attachment regions using cloned DNA.

Animals↗
PubMed2006

Computational study of matrix-peptide interactions in MALDI mass spectrometry: Interactions of 2,5- and 3,5-dihydroxybenzoic acid with the tripeptide valine-proline-leucine.

The mechanism of matrix-to-analyte proton transfer in matrix-assisted laser desorption and ionization mass spectrometry (MALDI-MS) has been investigated computationally by modeling the matrix-analyte interaction of potential MALDI matrixes such as 2,5-dihydroxybenzoic acid (2,5-DHB) and 3,5-DHB with the tripeptide valine-proline-leucine (VPL). A combination of molecular dynamics/simulated annealing calculations followed by density functional theory geometry optimization using a reasonably large basis set has been done on a large number of clusters in an attempt to study the ionization energy of each matrix in the cluster environment and the intracluster proton transfer from the matrix to the tripeptide. The calculations show a substantial reduction in the IP for both matrixes in their cluster environments. In the 2,5-system, proton transfer can sometimes occur in the neutral clusters (preformed ions), whereas proton transfer in the cationic clusters, which is actually a double proton transfer, is spontaneous and exoergic. Even though it is more acidic from a thermodynamic perspective, the radical cation of 3,5-DHB is a less efficient proton donor to VPL. The thermodynamics of proton transfer in the cationic clusters is discussed in detail.

Computational Biology↗
PubMed1997

Proteinases and myocardial extracellular matrix turnover.

Extracellular structural remodeling is the compensatory response of the tissue following pathological stage. Myocardial infarction, which leads to adverse remodeling, thinning of the ventricle wall, dilatation and heart failure, is one of the leading causes of death. Remodeling implies an alteration in the extracellular matrix and in the spatial orientation of cells and intracellular components. The extracellular matrix is responsible for cardiac cell alignment and myocardial structural integrity. Substances that break down the extracellular matrix, specialized proteinases as well as inhibitors of proteinases, appear to be normally balanced in maintaining the integrity of the myocardium. Myocardial infarction leads to an imbalance in proteinase/antiproteinase activities causing alterations in the stability and integrity of the extracellular matrix and adverse tissue remodeling. To explore mechanisms involved in this process and, in particular, to focus on matrix metalloproteinases, their inhibitors, and activators, an understanding of proteinase and antiproteinase is needed. This review represents new and significant information regarding the role of activated matrix proteinases antiproteinases in remodeling. Such information will have a significant impact both on the understanding of the basic cell biology of extracellular matrix turnover, as well as on potential avenues for pharmacological approaches to the treatment of ischemic heart disease and failure.

Amino Acid Sequence↗
PubMed1992

Interactions of LDL and modified LDL with mesangial cells and matrix.

Hyperlipidemia may play a role in the progression of diabetic and other renal diseases. Low density lipoprotein (LDL) and other proteins including extracellular matrix components undergo nonenzymatic glycation in vivo. We examined the effects of glycation of LDL as occurs in diabetes (4 to 8%) on binding and uptake by mesangial cells and their proliferation. The glycation of LDL (g-LDL) significantly decreased its binding and uptake by mesangial cells by 15 to 20%, indicating that glycated LDL binds to the LDL receptor, but with lower affinity than LDL. Both LDL and g-LDL modestly stimulated [3H] thymidine incorporation into mesangial cells at 5 to 10 micrograms/ml. Native, oxidized (Ox-LDL) and glycated LDL all bound to the extracellular matrix generated by rat mesangial cells in culture. The binding of LDL, Ox-LDL and g-LDL to mesangial matrix was two to four times higher than to mesangial cells. Binding of LDL and g-LDL was significantly higher to glycolaldehyde modified matrix, which serves as an in vitro model for nonenzymatic glycation end-product cross-linking of matrix which occurs in long-standing diabetes. Based on these findings, we propose that glycation of LDL decreases its binding and uptake by the LDL receptor of mesangial cells and may slow its catabolism. Furthermore, LDL bound to extracellular mesangial matrix can undergo oxidation and generate cytotoxic LDL components. This process may be further enhanced by advanced glycation of the mesangial matrix in diabetes, contributing to glomerular pathology.

Animals↗
PubMed2002

Keratinocyte stimulation of matrix metalloproteinase-1 production and proliferation in fibroblasts: regulation through mitogen-activated protein kinase signalling events.

Incubation of human dermal fibroblasts in keratinocyte-conditioned culture medium led to a 5.7-fold increase in the level of matrix metalloproteinase-1. Virtually all of the matrix metalloproteinase-1 - inducing activity could be related to agonists acting through members of the epidermal growth factor receptor family or to agonists acting through the interleukin-1 receptor. The same keratinocyte-conditioned medium also induced a modest increase in fibroblast proliferation (approximately 1.8-fold). Growth-stimulating activity could be attributed to epidermal growth factor receptor (but not interleukin-1 receptor) function. In fibroblasts exposed to keratinocyte-conditioned medium, mitogen-activated protein kinase signalling through both the extracellular signal-related kinase pathway and p38 pathway occurred. When recombinant epidermal growth factor or recombinant interleukin-1beta were used as a control, they induced mitogen-activated protein kinase signalling consistent with the combined effects of epidermal growth factor receptor - specific and interleukin-1 receptor - specific agonists in keratinocyte-conditioned medium. Recombinant epidermal growth factor stimulated both matrix metalloproteinase-1 induction and proliferation while recombinant interleukin-1beta stimulated matrix metalloproteinase-1 elaboration but not fibroblast growth. An inhibitor of extracellular signal-related kinase pathway signalling (U0126) blocked induction of matrix metalloproteinase-1 production induced by keratinocyte-conditioned medium (as well as by epidermal growth factor or interleukin-1beta), and also inhibited proliferation. A p38 signalling inhibitor (SB203580) blocked matrix metalloproteinase-1 elaboration induced by keratinocyte-conditioned medium or interleukin-1beta, but did not inhibit matrix metalloproteinase-1 elaboration or cell growth induced by epidermal growth factor. These data indicate that keratinocyte-fibroblast interactions are mediated by multiple stimulating agents acting on specific receptors to induce signalling through different mitogen-activated protein kinase pathways leading to altered expression of key biological functions.

Carrier Proteins↗