SEARCH · PubMed Health

Results for “Extracellular Matrix”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 163 records · Page 9Linked to original sources

PubMed2001

Tumorigenic potential of extracellular matrix metalloproteinase inducer.

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs.

Animals↗

PubMed1994

[The extracellular matrix: from supporting tissue to regulation of cytokines].

Extracellular matrix is a polymorphic structure composed of at least thirty molecules (collagens, glycoproteins, elastin, and proteoglycans) associated in a complex network. This insoluble structured framework ensures tissue cohesiveness, and allows cells to adhere, migrate and interact. Together with cytokines extracellular matrix is also involved in the control of various aspects of cell activities. Cytokines mediate cell to cell communication. Their broad effect result from their pleiotropic and overlapping activities. Once secreted, these molecules diffuse between cells--i.e. across extracellular matrix--to reach their target cells. An increasing number of cytokines are now known to bind to the extracellular matrix. These interactions change the availability of cytokines on effector cells, activate some growth factors, localize and/or increase the duration of the expected effect. Matrix-cytokines interactions are a new field of investigation which has changed our view on extracellular matrix. First considered as a supporting tissue, extracellular matrix appears now to be critically involved in the regulation of cytokine activities.

Cell Communication↗

PubMed1995

The role of extracellular matrix in injury to gastric mucosa by indomethacin.

The extracellular matrix components fibronectin, collagen IV, and laminin provide structural support for the gastric mucosal cells and influence cell migration, attachment, differentiation, and proliferation. Because little is known about the effect of indomethacin on the extracellular matrix, we studied the expression and distribution of extracellular matrix components in the gastric mucosa before and sequentially during indomethacin injury. A total of 32 male Sprague-Dawley rats were treated with placebo or indomethacin 100 mg intraperitoneally. One, 4, and 18 h later, stomachs were excised and gastric specimens were immunostained with specific antibodies against fibronectin (FN), collagen IV (CIV), laminin (LM), fibronectin receptor (FNR), and vimentin (VM). Gross necrosis, quantitative histology, and expression of FN, CIV, LM, FNR, and VM were analyzed using a videoimage analysis system. In the mucosa treated with indomethacin, the expression of VM and LM was decreased by 54% (p < 0.01) and 52% (p < 0.01), respectively, within 1 h vs. control mucosa. The former reflected damage to endothelial cells. Expression of FN, FNR, and CIV was decreased by 50, 25, and 50%, respectively, at 1 h after indomethacin, reflecting significant damage to the extracellular matrix. However, at 1 h, no gross necrosis and no histologic damage were seen in the gastric mucosa. We conclude that expression of extracellular matrix components in the gastric mucosa is significantly reduced during indomethacin injury and that damage to extracellular matrix and microvascular endothelium precedes injury of glandular epithelial cells.

Animals↗

PubMed2005

Extracellular matrix changes regulate calcium crystal formation in articular cartilage.

PURPOSE OF REVIEW: The pathologic matrix mineralization seen in calcium pyrophosphate dihydrate and basic calcium phosphate deposition diseases identifies a subset of osteoarthritis patients with an unusual joint distribution and rapid progression of disease. Several factors contribute to pathologic matrix mineralization, including changes in the extracellular matrix of articular cartilage. The factors contributing to extracellular matrix changes that promote crystal formation are important and not well understood. Better characterization of these factors will enhance the understanding of the pathogenesis of pathologic matrix mineralization and may identify potential targets for novel therapeutic interventions. RECENT FINDINGS: Histologic studies of cartilage from patients affected by calcium crystal arthritis show changes in the pericellular matrix of articular chondrocytes. The amounts and types of collagens, proteoglycans, and calcium-binding proteins are altered. The mechanisms by which these changes occur remain poorly understood. Recent work, however, has implicated alterations in the chondrocyte phenotype and post-translational matrix-modulating enzymes such as the transglutaminases. SUMMARY: Changes in extracellular matrix are associated with the pathologic matrix mineralization seen in calcium pyrophosphate dihydrate and basic calcium phosphate crystal deposition diseases. The literature on growth plate cartilage provides observations and mechanisms through which extracellular matrix contributes to normal matrix mineralization, and has served as a model on which to base studies in articular cartilage. More studies are warranted to enhance the understanding of how changes in extracellular matrix contribute to crystal deposition diseases.

Calcium Phosphates↗

PubMed2006

Extracellular matrix remodeling in canine and mouse myocardial infarcts.

Extracellular matrix proteins not only provide structural support, but also modulate cellular behavior by activating signaling pathways. Healing of myocardial infarcts is associated with dynamic changes in the composition of the extracellular matrix; these changes may play an important role in regulating cellular phenotype and gene expression. We examined the time course of extracellular matrix deposition in a canine and mouse model of reperfused infarction. In both models, myocardial infarction resulted in fragmentation and destruction of the cardiac extracellular matrix, extravasation of plasma proteins, such as fibrinogen and fibronectin, and formation of a fibrin-based provisional matrix providing the scaffold for the infiltration of granulation tissue cells. Lysis of the plasma-derived provisional matrix was followed by the formation of a cell-derived network of provisional matrix composed of cellular fibronectin, laminin, and hyaluronic acid and containing matricellular proteins, such as osteopontin and osteonectin/SPARC. Finally, collagen was deposited in the infarct, and the wound matured into a collagen-based scar with low cellular content. Although the canine and mouse infarcts exhibited a similar pattern of extracellular matrix deposition, deposition of the provisional matrix was more transient in the mouse infarct and was followed by earlier formation of a mature collagen-based scar after 7-14 days of reperfusion; at the same timepoint, the canine infarct was highly cellular and evolving. In addition, mature mouse infarcts showed limited collagen deposition and significant tissue loss leading to the formation of a thin scar. In contrast, dogs exhibited extensive collagen accumulation in the infarcted area. These species-specific differences in infarct wound healing should be taken into account when interpreting experimental infarction studies and when attempting to extrapolate the findings to the human pathological process.

Animals↗

PubMed2000

Dm1-MMP, a matrix metalloproteinase from Drosophila with a potential role in extracellular matrix remodeling during neural development.

We have cloned and characterized a cDNA encoding Dm1-MMP, the first matrix metalloproteinase (MMP) identified in Drosophila melanogaster. The isolated cDNA encodes a protein of 541 residues that has a domain organization identical to that of most vertebrate MMPs including a signal sequence, a prodomain with the activation locus, a catalytic domain with a zinc-binding site, and a COOH-terminal hemopexin domain. Northern blot analysis of Dm1-MMP expression in embryonic and larval adult tissues revealed a strong expression level in the developing embryo at 10-22 h, declining thereafter and being undetectable in adults. Western blot analysis confirmed the presence of pro- and active forms of Dm1-MMP in vivo during larval development. In situ hybridization experiments demonstrated that Dm1-MMP is expressed in a segmented pattern in cell clusters at the midline during embryonic stage 12-13, when neurons of the central nervous system start to arise. Recombinant Dm1-MMP produced in Escherichia coli exhibits a potent proteolytic activity against synthetic peptides used for analysis of vertebrate MMPs. This activity is inhibited by tissue inhibitors of metalloproteinases and by synthetic MMP inhibitors such as BB-94. Furthermore, Dm1-MMP is able to degrade the extracellular matrix and basement membrane proteins fibronectin and type IV collagen. On the basis of these data, together with the predominant expression of Dm1-MMP in embryonic neural cells, we propose that this enzyme may be involved in the extracellular matrix remodeling taking place during the development of the central nervous system in Drosophila.

Amino Acid Sequence↗

PubMed1982

Preparation of cell-free extracellular matrix from human peripheral nerve.

The extracellular matrix of human peripheral nerve, which is mainly basement membrane and fibrillar collagen, has been prepared by a procedure involving extensive detergent extraction of isolated endoneurium and perineurium obtained from various nerves. The ultrastructure of the isolated nerve extracellular matrix was indistinguishable from that seen in sections of intact nerve, indicating that the extraction procedure preserved the morphological integrity of these connective tissue components. The amino acid and carbohydrate compositions of the nerve extracellular matrix preparations were typically collagenous in nature containing a high content of glycine, proline, 4-hydroxyproline, and alanine and significant amounts of lysine and hydroxylysine. The preparations contained virtually no 3-hydroxyproline and low content of glucose and galactose compared to pure basement membranes, indicating that interstitial rather than basement membrane collagens predominated. This preparation appears well-suited to both the ultrastructural and biochemical study of the extracellular matrix of peripheral nerve.

Cell Fractionation↗

PubMed1998

Extracellular matrix changes in human corneas after radial keratotomy.

Extracellular matrix and basement membrane alterations were identified in human corneas after radial keratotomy. Ten normal and five radial keratotomy autopsy corneas (two at 6 months post surgery, and three at 3 years post surgery) were studied by immunofluorescence with antibodies to 28 extracellular matrix and basement membrane components. Outside of radial keratotomy scars, all studied components had a normal distribution. Of stromal extracellular matrix, only type III collagen accumulated around the scars. The basement membrane around epithelial plugs had a normal composition except for type IV collagen. Its alpha1-alpha2 chains, normally present only in the limbal basement membrane, appeared around all plugs. alpha3 and alpha4 chains were very weak or absent in these areas, contrary to nonscarred areas. This basement membrane pattern was similar to the normal limbal but not to the central corneal pattern. Keratin 3 also had a limbal-like, suprabasal expression in the plug epithelium. The stroma around the scars accumulated tenascin-C, fibrillin-1, types VIII and XIV collagen, all of which were absent from normal corneal basement membrane and extracellular matrix. Only tenascin-C showed less staining in anterior scars 3 years post surgery than 6 months post surgery, but still persisted in posterior scars. Incomplete scar healing was evident even 3 years post radial keratotomy. It was manifested by the accumulation of abnormal extracellular matrix in the anterior and posterior scars and by the limbal-like pattern of type IV collagen isoforms in the basement membrane around epithelial plugs.

Adult↗

PubMed2006

Extracellular matrix in disc degeneration.

The extracellular matrix of the intervertebral disc structures contains many molecules also found in cartilage. The extremely polyanionic proteoglycans play a central role, particularly in the nucleus, by creating an osmotic environment leading to retention of water and ensuing resistance to deformation-important for the resilience of the tissue. Another major structural entity particularly important in the anulus is the network of collagen fibers; fibril-forming collagen 1 is a major constituent. The collagen fibrils in the anulus are largely oriented in sheets around the nucleus. A number of molecules present in the matrix regulate and direct the collagen fibril assembly by interacting with the collagen molecule and also the formed fibril. Several of these molecules bind by one domain to the collagen fiber and present another functional domain to interact either with other fibers or with other matrix constituents. In this manner the collagen fibers are cross-linked into a network that provides tensile strength and distributes load over large parts of the anulus. Diminished function in these cross-bridging molecules will lead to loss of mechanical properties of the collagen network and result in an impaired ability of the anulus to resist forces delivered by compression of the disc and particularly the nucleus. A different network abundant in the disc and in other load-bearing tissues is based on the beaded filaments of collagen 6. The basic building block is a tetramer of two pairs of antiparallel collagen-6 molecules arranged such that two N-terminal ends of collagen 6 are exposed at either end of the unit. Further assembly occurs both by end-to-end and side-to-side associations. This process is catalyzed by both biglycan and decorin, where the combined effect of direct binding of the core protein to the collagen-6 N-terminal globular domain and the presence of the glycosaminoglycan side chain is essential. These ligands are bound at the same site in complexes extracted from the tissue and then also have one bound molecule of matrilin-1, 2, or 3, in turn bound to a collagen fiber, a procollagen molecule, or an aggrecan. Interactions at the cell surface provide signals to the cells with regard to the conditions of the matrix. Such interactions include binding by matrix components to various receptors at the cell surface. Remodeling of the matrix takes place in response to various factors. An early event in disease is degradation of aggrecan by the members of the ADAMTS (a disintegrin-like and metalloprotease with thrombospondin motifs) family and degradation of molecules important in maintaining the collagen network.

Cartilage Oligomeric Matrix Protein↗

PubMed2004

Regulation of matrix metallo-proteinase expression by extracellular matrix components in cultured hepatic stellate cells.

Hepatic stellate cells (HSC) changed their morphology and function including production of matrix metalloproteinases (MMPs) in response to extracellular matrix (ECM) component used as a substratum in culture. We examined in this study the regulatory role of ECM component on expression of MMPs and tissue inhibitor of metalloproteinase (TIMP) in rat HSCs cultured on polystyrene, type I collagen-coated surface, type I collagen gel, or Matrigel, respectively. When cultured on type I collagen gel, HSCs showed the asteroid cell shape and MMP-1 activity, as detected by in situ zymography. Expression of MMP-1 protein and mRNA were examined by using immunofluorescence staining and RT-PCR analysis in HSCs cultured on type I collagen gel. Active form of MMP-2 was detected by gelatin zymography in the conditioned medium of HSCs cultured on type I collagen gel, whereas it was not detected when HSCs were cultured on polystyrene, type I collagen-coated surface, or Matrigel. Increased MMP-2 mRNA was detected by RT-PCR in HSCs cultured on type I collagen gel. Increased MT1-MMP proteins were shown to localize on the cell membrane by using immunofluorescence staining in HSCs cultured on type I collagen gel. Elevated expression of membrane-type matrix metallproteinase-1 (MT1-MMP) mRNA and tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA was detected by RT-PCR in HSCs cultured on type I collagen-coated surface or type I collagen gel. These results indicate that expression of MMPs and TIMP-2 is regulated by ECM components in cultured HSCs, suggesting an important role of HSCs in the remodeling of liver tissue.

Journal Article↗

PubMed2002

Pseudomonas aeruginosa binds to extracellular matrix deposited by human corneal epithelial cells.

PURPOSE: To measure the effect of extracellular matrix substrate, pH, and O(2) on Pseudomonas aeruginosa binding. METHODS: Extracellular matrix substrates were prepared from human corneal epithelial cells cultured in 2% or 20% O(2). P. aeruginosa strains ATCC 19660 or PAO1 (suspended in pH 7.0 or 7.5 buffer) were cultured on extracellular matrix substrates in 2% or 20% O(2). The mean number of adherent bacteria per counted per field +/- SEM (n = 15) was determined for combinations of bacteria, extracellular matrix substrate, pH, and O(2). Binding in the presence of antibodies directed against laminin-5 was also measured. RESULTS: Extracellular matrix substrates produced by cells cultured in 20% O(2), combined with an environment of pH 7.0, provided the least favorable conditions for binding of strain 19660. In contrast, extracellular matrix substrates produced by cells cultured in 2% O(2), combined with an environment of pH 7.0, provided the most favorable conditions for binding of strain 19660. Binding of PAO1, however, as a function of extracellular matrix substrate and pH, did not similarly compare with binding of strain 19660. Antibodies against laminin-5 chains served to increase the number of strain 19660 bacteria bound to extracellular matrix substrates compared with the control. CONCLUSIONS: The extracellular matrix secreted by hypoxic corneal epithelial cells is a substrate for binding of P. aeruginosa. Results in previous studies have shown that hypoxic extracellular matrix contains less laminin-5 protein than normoxic matrix. The antibody studies in this report suggest that the decrease in laminin-5 content in hypoxic matrix, relative to matrix secreted by normoxic corneal epithelium, may be responsible for increased bacterial adhesion.

Adolescent↗

PubMed1990

Proliferative response and macromolecular synthesis by ocular cells cultured on extracellular matrix materials.

To investigate the effects of extracellular matrix components on cellular function, we cultured several types of ocular cells on substrates composed of extracellular matrix materials that were layered on culture dishes either as dried films or as gels. We measured cellular proliferation on these substrates and on a series of gels composed of varying proportions of rat tail tendon type I collagen and Matrigel, a commercially available extract of a basement membrane-producing murine tumor. In addition, we studied the biosynthesis of collagens and of proteoglycans by these cultured cells using [3H]-L-proline and [35S]-sulfate. The proliferative abilities of the various types of ocular cells on the dried film substrates, on uncoated plastic culture vessels, and on pure type I collagen gel, were similar. However, proliferation of ocular cells cultured on gels composed of greater than or equal to 90% Matrigel was markedly reduced. There was little or no inhibition of growth of two types of non-ocular cells: rat C6 astrocytoma cells, and human dermal fibroblasts. Histologic studies showed that the ocular cells tested often formed long strands and capillary-like tubes, and tended to "burrow" beneath the surface of substrates containing high percentages of Matrigel. Fibroblasts infrequently formed tubes, and exhibited the burrowing property also on gels containing primarily type I collagen, while C6 cells showed neither of these behaviors on any of the matrices tested. The elution pattern of newly synthesized [3H]-labeled and [35S]-labeled macromolecules produced by all of the cultured cell types, and detected by Sepharose CL-4B chromatography in the medium and in the cell layer plus matrix fractions did not vary following culture on the different substrates. Approximately twofold more of the newly synthesized collagens and proteoglycans were deposited in the cell layer plus matrix, and proportionately less appeared in the medium, when cells were cultured on type I collagen gels and on Matrigel than on the dried film substrates. These experiments demonstrate the influence of the extracellular matrix on several aspects of cell behavior, and provide further evidence that modification of the composition of the extracellular matrix may be an important determinant of normal or pathological cell function.

Animals↗

PubMed2006

Extracellular matrix of the human cyclic corpus luteum.

Extracellular matrix regulates many cellular processes likely to be important for development and regression of corpora lutea. Therefore, we identified the types and components of the extracellular matrix of the human corpus luteum at different stages of the menstrual cycle. Two different types of extracellular matrix were identified by electron microscopy; subendothelial basal laminas and an interstitial matrix located as aggregates at irregular intervals between the non-vascular cells. No basal laminas were associated with luteal cells. At all stages, collagen type IV alpha1 and laminins alpha5, beta2 and gamma1 were localized by immunohistochemistry to subendothelial basal laminas, and collagen type IV alpha1 and laminins alpha2, alpha5, beta1 and beta2 localized in the interstitial matrix. Laminin alpha4 and beta1 chains occurred in the subendothelial basal lamina from mid-luteal stage to regression; at earlier stages, a punctate pattern of staining was observed. Therefore, human luteal subendothelial basal laminas potentially contain laminin 11 during early luteal development and, additionally, laminins 8, 9 and 10 at the mid-luteal phase. Laminin alpha1 and alpha3 chains were not detected in corpora lutea. Versican localized to the connective tissue extremities of the corpus luteum. Thus, during the formation of the human corpus luteum, remodelling of extracellular matrix does not result in basal laminas as present in the adrenal cortex or ovarian follicle. Instead, novel aggregates of interstitial matrix of collagen and laminin are deposited within the luteal parenchyma, and it remains to be seen whether this matrix is important for maintaining the luteal cell phenotype.

Collagen Type IV↗

PubMed1993

Growth and degeneration of axons on astrocyte surfaces: effects on extracellular matrix and on later axonal growth.

Cultured astrocytes deposit an extracellular matrix which has been shown by immunocytochemistry to react with antibodies to tenascin, laminin, and fibronectin. Neuronal-glial interaction down-regulates these components of the matrix, causing a reduction in extracellular matrix localized to areas of contact with axons. Axons used for these experiments were from embryonic rat retinal explants. In some experiments explants were removed from the co-cultures and their axons allowed to degenerate. Degeneration of axons did not reverse the local reduction of extracellular matrix brought about by axon outgrowth. The period of axon outgrowth studied was 4-5 days; the period of degeneration was 2-3 days. Astrocytes alone, astrocytes with intact retinal explants, and astrocytes with 2-day degenerated retinal axons were tested for their ability to support neurite outgrowth from embryonic rat cortical neurons. Neurite outgrowth occurred on all astrocyte cultures. Cortical neurite lengths, measured 2 days after plating, were not significantly different between astrocytes alone and astrocytes with degenerated retinal axons. However, there was a tendency for neurites to be shorter on astrocytes with intact retinal axons present. Two conclusions may be drawn from these results. First, the state of differentiation of astrocytes, as marked by their assembly of extracellular matrix, is altered by contact with axons. Second, degeneration of axons alone, in the absence of other cell types, is not a sufficient signal to reestablish assembly of extracellular matrix. However, neither is it a sufficient signal to render astrocytes inhospitable to further axonal outgrowth or regeneration.

Animals↗

PubMed1987

Inhibition of growth and induction of differentiation in a malignant human glioma cell line by normal leptomeningeal extracellular matrix proteins.

We devised a model system to study the effects of extracellular matrix proteins on the malignant phenotype of an anaplastic glioma cell line, U 343 MG-A. Well-characterized cultures derived from normal human leptomeninges were grown to confluence and maintained for 2 weeks. The leptomeningeal cells were then removed with base and detergent, leaving behind an extracellular matrix enriched in laminin, fibronectin, type I and IV collagen, and procollagen III. U 343 MG-A tumor cells planted on top of this normal extracellular matrix were profoundly growth inhibited compared with glioma cells grown on plastic alone. Glioma cells grown on the extracellular matrix developed multiple, slender processes and assumed a more differentiated astrocytic phenotype; immunostains for glial fibrillary acidic protein revealed a more extensive intracytoplasmic network of intensely staining filaments than in control glioma cells. When glioma cells grown on the extracellular matrix were analyzed by an enzyme-linked immunosorbent assay for glial fibrillary acidic protein, the amount of this intermediate filament per cell was increased 20-fold compared with glioma cells growing on plastic. The growth and differentiation of U 343 MG-A glioma cells in flasks coated with purified fibronectin or laminin was not significantly perturbed; however, glioma cell cultures grown in flasks coated with purified type I or IV collagen showed decreased cellular proliferation, stellate cell formation, and increased levels of glial fibrillary acidic protein per cell compared with glioma cells growing on plastic. Gelatin gel analysis showed that U 343 MG-A glioma cells growing on plastic secreted a 65,000-D metalloproteinase that was not secreted by glioma cells grown on the leptomeningeal extracellular matrix. We conclude that in this system, the extracellular matrix of a normal human leptomeningeal culture substantially inhibited the proliferation of and induced differentiation in an anaplastic glioma cell line. Our analysis of single components of the extracellular matrix suggests that these effects may be mediated in part by type I and IV collagen. The mechanism by which the leptomeningeal extracellular matrix inhibits glioma cell proliferation may be by diminishing tumor-associated protease secretion so that the degradation of extracellular matrix macromolecules in the tumor cell microenvironment is prevented and tumor cell migration becomes less likely.

Cell Differentiation↗

PubMed1999

Composition of the extracellular matrix in human cricoarytenoid joint articular cartilage.

The extracellular matrix of the human cricoarytenoid joint articular cartilage is involved in different pathological changes. Interestingly, in contrast to the limb joints, the extracellular matrix composition of the healthy cricoarytenoid joint articular cartilage has not yet been elucidated except by some light microscopical investigations. The present study investigates the extracellular matrix components of the cricoarytenoid joint articular cartilage by means of light microscopy, immunohistochemistry, transmission electron microscopy and scanning electron microscopy and compares them with the limb joints for a better understanding of their involvement in joint disease. Chondrocytes near the joint surface of the cricoid and arytenoid cartilage differ from chondrocytes of deeper cartilage layers. The extracellular matrix of the articular cartilage contains chondroitin-4-sulfate, chondroitin-6-sulfate and keratansulfate as well as collagen types II, III, VI, IX and XI. Type-III-collagen shows a special distribution throughout the joint cartilage. In deeper cartilage layers, type-III-collagen occurs only pericellularly; in higher cartilage layers type-III-collagen is also located territorially and interterritorialy in small amounts. Scanning and transmission electron microscopy have revealed the articular surface of the cricoid and arytenoid cartilage to consist of a network of irregularly organized collagen fibrils, which are lined by a layer of electron dense material. The network coats subjacent collagen bundles which descend obliquely downward and intermingle at right angles in the middle part of the articular cartilage with collagen bundles of the deeper cartilage zones. The articular cartilage surface shows structural characteristics which differ from the underlying cartilage. The superficial electron dense layer possibly plays a role in the lubrication of the articular cartilage surface. The alignment of the fibrillar structures in the articular cartilage of the cricoarytenoid joint varies from those of the limb joints based on the different strain occurring during arytenoid movement. Nevertheless, the human cricoarytenoid joint articular cartilage can be compared with the joints of the limbs despite its extracellular matrix composition and its involvement in joint pathology. Evidence of type III collagen in the outermost layer of the articular cartilage of the cricoarytenoid joint presents a peculiarity, which has yet not be demonstrated in the articular cartilage of limb joints.

Adult↗

PubMed2004

Tissue repair and the dynamics of the extracellular matrix.

Repair of tissue after injury depends on the synthesis of a fibrous extracellular matrix to replace lost or damaged tissue. Newly deposited extracellular matrix is then re-modeled over time to emulate normal tissue. The extracellular matrix directs repair by regulating the behavior of the wide variety of cell types that are mobilized to the damaged area in order to rebuild the tissue. Acute inflammation, re-epithelialization, and contraction all depend on cell-extracellular matrix interactions and contribute to minimize infection and promote rapid wound closure. Matricellular proteins are up-regulated during wound healing where they modulate interactions between cells and the extracellular matrix to exert control over events that are essential for efficient tissue repair. Here, we discuss how the extracellular matrix changes during the stages of tissue repair, how matricellular proteins affect cell-extracellular matrix interactions, and how these proteins might be exploited for use therapeutically.

Animals↗

PubMed1998

Regulation of mammary differentiation by extracellular matrix involves protein-tyrosine phosphatases.

Extracellular matrix and growth factors cooperate to regulate signaling pathways and gene transcription in adherent cells. However, the mechanism of extracellular matrix signaling is poorly defined. In mammary gland, the expression of milk protein genes is controlled by cross-talk between signals derived from the basement membrane protein, laminin, and the lactogenic hormone, prolactin. Signals from basement membrane are transduced by beta1 integrins and are required for prolactin to activate DNA binding of the milk protein gene transcription factor, Stat5. Here we show that basement membrane is necessary for tyrosine phosphorylation of the prolactin receptor and thus directly affects cytokine signaling and differentiation at the level of the plasma membrane. Prolactin does not induce tyrosine phosphorylation of its receptor, Jak2, or Stat5 in nondifferentiated breast epithelia cultured on collagen I, and we show that this is due to a vanadate-sensitive activity that inhibits the prolactin pathway. We suggest that protein-tyrosine phosphatases are novel targets for regulation by extracellular matrix and in mammary cells represent an additional control to the requirement of integrins for milk protein production.

Animals↗