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PubMed2006

Response of matrix metalloproteinase-9 to olfactory nerve injury.

Matrix metalloproteinases function in the remodeling of the extracellular matrix during growth and development as well as in injury and disease processes. We examined the role of matrix metalloproteinase-9 in a model of olfactory nerve injury in mice. We measured changes in matrix metalloproteinase-9 protein levels for up to 60 days following olfactory nerve transection. Matrix metalloproteinase-9 levels increased within hours after injury, peaked at day 1 and were elevated for approximately 2 weeks before returning to control levels over the 60-day time period. The increase in matrix metalloproteinase-9 was temporally associated with the degeneration of olfactory neurons that follows nerve transection and with increased gliosis. Our results demonstrate a temporal relationship between matrix metalloproteinase-9 elevation, degeneration of olfactory neurons and gliosis.

Animals↗
PubMed1994

Effects of epidermal growth factor on invasiveness through the extracellular matrix in high- and low-metastatic clones of RCT sarcoma in vitro.

We investigated the invasiveness of tumor cells through the extracellular matrix and the influence of epidermal growth factor (EGF) on tumor cell invasion using in vitro systems in high-[RCT(+)] and low-metastatic [RCT(-)] clones established from poorly differentiated murine RCT sarcoma in C3H/He mice. In the invasion assay using a filter coated with reconstituted basement membrane (Matrigel) in a Boyden chamber, RCT(+) cells were more invasive than RCT(-) cells. The attachment of RCT(+) cells to extracellular matrix components and the degradation of type IV collagen by the cells were significantly greater than with RCT(-) cells. However, there was no significant difference in the migration of cells to the extracellular matrix components between cultured RCT(+) and RCT(-) cells. These findings suggested that the different invasiveness of these clone cells was associated with the difference in the ability of attachment to and degradation of the matrix. The level of laminin receptor expression in RCT(+) cells was about four-fold that in RCT(-) cells and laminin stimulated the type IV collagenolytic activity of RCT(+) cells, suggesting that RCT(+) cell attachment to laminin via laminin receptor on the cell surface induced the production of type IV collagenase by the tumor cells. EGF did not affect the invasiveness of RCT(-) cells. In RCT(+) cells, EGF stimulated the invasiveness through Matrigel, the attachment to extracellular matrix components and the degradation of type IV collagen through high-affinity EGF receptors (EGFR), with Kd of pM order, while the migration to the matrix was not influenced by EGF. These findings suggest that the stimulatory effect of EGF on invasion is related to the acceleration of cell adhesion, and the degradative cascade of the extracellular matrix and high-affinity EGFRs play an important role in the effect of EGF on in vitro invasiveness in this tumor.

Animals↗
PubMed1994

Characterisation of two intronic nuclear-matrix-attachment regions in the human DNA topoisomerase I gene.

We identify two high-affinity matrix-attachment regions (MAR elements) located in two introns of the human DNA topoisomerase I gene (TOP1). These intronic MAR elements, designated MI and MII, are specifically bound by the nuclear matrix and partition with scaffolds in vitro. One of these MAR elements, MII, is part of a genomic region which is hypersensitive for endogenous nucleases. We have sequenced both DNA elements and have characterized their mode of binding to the nuclear matrix. Experiments with the minor-groove-binding ligands distamycin and chromomycin indicate that the A+T-rich regions, most likely homopolymeric A tracts, are responsible for binding of these DNA elements to the nuclear matrix. MII contains an alu-like element and a segment of curved DNA. Analysis of subfragments of MII show that the curved DNA region itself shows only weak nuclear-matrix binding, and that the high-affinity binding sites are located on subfragments on the 5' side of the curved DNA. In addition, we found that the alu-like sequence does not contribute significantly to the binding of MII and of subfragments of MII to nuclear-matrix proteins. Comparing the distribution of repetitive sequences in the cloned parts of human DNA topoisomerase I gene with the location of high-affinity matrix-binding sites we find no evidence that repetitive DNA may be located close to MAR elements as has been previously suggested.

Binding Sites↗
PubMed1998

Effects of ethanol on gene expression in rat bone: transient dose-dependent changes in mRNA levels for matrix proteins, skeletal growth factors, and cytokines are followed by reductions in bone formation.

Several studies were performed in female rats to determine dose and time course changes in mRNA levels for matrix proteins in bone after a single administration of ethanol. As expected, dose-dependent transient increases in blood ethanol were measured. Additionally, there was mild hypocalcemia with no change in immunoreactive parathyroid hormone. Coordinated dose-dependent increases in mRNA for type 1 collagen, osteonectin, and osteocalcin were noted in the proximal tibial metaphysis 6 hr after ethanol was given, with the peak values occurring at a dose of 1.2 g/kg (0.4 ml). Similar increases in mRNA levels for matrix proteins were noted in lumbar vertebrae after ethanol treatment. The changes were specific for bone; ethanol had no effect on mRNA levels for matrix proteins in the uterus or liver, although the mRNA concentrations tended to be reduced in uterus. Message levels for several cytokines implicated in the regulation of bone turnover were also assayed; mRNA levels for transforming growth factor-beta1, transforming growth factor-beta2, interferon-gamma, and interleukin-6 were unchanged at doses ranging from 0.14 to 1.7 g/kg. At the highest dose of ethanol, the mRNA level for tumor necrosis factor-alpha was elevated while the level for insulin-like growth factor-1 was reduced. The time course effects of ethanol (0.4 ml dose) were determined in a separate experiment. Ethanol resulted in a transient increase in mRNA levels for the three bone matrix proteins assayed. However, matrix protein synthesis, as determined by incorporation of 3H-proline into the proximal tibial metaphysis, was not changed after 6 hr. The changes in mRNA levels for the matrix proteins were preceded by brief, transient decreases in mRNA levels for interleukin-1beta, interferon-gamma, and migration inhibitory factor, and followed by a more prolonged decrease in the mRNA level for insulin-like growth factor-1. A subsequent study was performed to determine the effects of repetitive daily treatment with ethanol on rat bone. After 7 days, there were highly significant decreases in the mRNA level for type 1 collagen, as well as decreased bone formation. These results suggest that ethanol may alter bone metabolism by disturbing signal transduction pathways that regulate the expression of genes for bone matrix proteins, skeletal growth factors, and cytokines.

Animals↗
PubMed2001

Estimation of bone matrix apparent stiffness variation caused by osteocyte lacunar size and density.

The role of osteocyte lacunar size and density on the apparent stiffness of bone matrix was predicted using a mechanical model from the literature. Lacunar size and lacunar density for different bones from different gender and age groups were used to predict the range of matrix apparent stiffness values for human cortical and cancellous tissue. The results suggest that bone matrix apparent stiffness depends on tissue type (cortical versus cancellous), age, and gender, the magnitudes of the effects being significant but small in all cases. Males had a higher predicted matrix apparent stiffness than females for vertebral cancellous bone (p< I0(-7)) and the difference increased with age (p =0.0007). In contrast, matrix apparent stiffness was not different between males and females forfemoral cortical bone and increased with age in both males (p < 0.0001) and females (p < 0.0364). Osteocyte lacunar density and size may cause significant gender and age-related variations in bone matrix apparent stiffness. The magnitude of variations in matrix apparent stiffness was small within the physiological range of lacunar size and density for healthy bone, whereas the variations can be profound in certain pathological cases. It was proposed that the mechanical effects of osteocyte density be uncoupled from their biological effects by controlling lacunar size in normal bone.

Adolescent↗
PubMed1984

Nucleotide sequence of the gene encoding respiratory syncytial virus matrix protein.

The amino acid sequence of the matrix protein of the human respiratory syncytial virus (RS virus) was deduced from the sequence of a cDNA insert in a recombinant plasmid harboring an almost full-length copy of this gene. It specifically hybridized to a single 1,050-base mRNA from infected cells. The recombinant containing 944 base pairs of RS viral matrix protein gene sequence lacked five nucleotides corresponding to the 5' end of the mRNA. The nucleotide sequence of the 5' end of the mRNA was determined by the dideoxy sequencing method and found to be 5' NGGGC, wherein the C residue is one nucleotide upstream of the cloned viral sequence. The initiator ATG codon for the matrix protein is embedded in an AATATGG sequence similar to the canonical PXXATGG sequence present around functional eucaryotic translation initiation codons. There is no conserved sequence upstream of the polyadenylate tail, unlike vesicular stomatitis virus and Sendai virus, in which four nucleotides upstream of the polyadenylate tail are conserved in all genes. There is no equivalent of the eucaryotic polyadenylation signal AAUAAA upstream of the polyadenylate tail. The matrix protein of 28,717 daltons has 256 amino acids. It is relatively basic and moderately hydrophobic. There are two clusters of hydrophobic amino acid residues in the C-terminal third of the protein that could potentially interact with the membrane components of the infected cell. The matrix protein has no homology with the matrix proteins of other negative-strand RNA viruses, implying that RS virus has undergone extensive evolutionary divergence. A second open reading frame potentially encoding a protein of 75 amino acids and partially overlapping the C terminus of the matrix protein was also identified.

Amino Acid Sequence↗
PubMed1993

Adenovirus precursor to terminal protein interacts with the nuclear matrix in vivo and in vitro.

The adenovirus precursor to the terminal protein (pTP), expressed in a vaccinia virus expression system or in native adenovirus, was assayed for its ability to interact with the nuclear matrix. Biochemical function was measured by determining the relative amount of pTP protein or of adenovirus DNA that remained associated with the nuclear matrix after extensive washing. pTP was retained on the matrix whereas beta-galactosidase was not, as assayed by quantitative immunoblot analysis. Nuclear matrix isolated from adenovirus-infected HeLa cells retained bound adenovirus DNA even when washed with 1 M guanidine hydrochloride; this interaction could be inhibited by added purified pTP protein. Analogous experiments with matrix isolated from HeLa cells infected with a recombinant vaccinia virus that expressed pTP showed a similar retention of pTP protein; this association could also be inhibited by added pTP protein. Binding of pTP to nuclear matrix isolated from uninfected cells was saturable, with an apparent Kd of 250 nM and an estimated 2.8 x 10(6) sites for pTP binding per cell nucleus. The association of pTP with matrix is postulated to help direct adenovirus replication complexes to the appropriate locale within the nucleus.

Adenoviridae↗
PubMed1994

Efficient particle formation can occur if the matrix domain of human immunodeficiency virus type 1 Gag is substituted by a myristylation signal.

Lentiviruses, such as human immunodeficiency virus type 1 (HIV-1), assemble at and bud through the cytoplasmic membrane. Both the matrix (MA) domain of Gag and its amino-terminal myristylation have been implicated in these processes. We have created HIV-1 proviruses lacking the entire matrix domain of gag which either lack or contain an amino-terminal myristate addition sequence at the beginning of the capsid domain. Myristate- and matrix-deficient [myr(-)MA(-)] viruses produced after transient transfection are still able to assemble into particles, although the majority do not form at the plasma membrane or bud efficiently. Myristylation of the amino terminus of the truncated Gag precursor permits a much more efficient release of the mutant virions. While myr(-)MA(-) particles were inefficient in proteolytic processing of the Gag precursor, myristylation enabled efficient proteolysis of the mutant Gag. All matrix-deficient viruses are noninfectious. Particles produced by matrix-deficient mutants contain low levels of glycoproteins, indicating the importance of matrix in either incorporation or stable retention of Env. Since matrix-deficient viruses contain a normal complement of viral genomic RNA, a role for MA in genomic incorporation can be excluded. Contrary to previous reports, the HIV-1 genome does not require sequences between the 5' splice donor site and the gag start codon for efficient packaging.

Base Sequence↗
PubMed1987

Culture of type II pneumocytes on a type II cell-derived fibronectin-rich matrix.

Recent evidence suggests that during primary culture, type II pneumocytes synthesize and deposit components of an extracellular matrix. The present study investigated the response of freshly isolated type II cells to a preformed, fibronectin-rich matrix synthesized by type II cells over a 6-day interval of primary culture on a plastic surface. Type II cells on 6-day matrix (M6) degraded the preformed matrix and deposited newly synthesized fibronectin more rapidly than cells on plastic, suggesting that M6 itself stimulated type II cell-mediated matrix turnover. In type II cells on plastic, incorporation of radiolabeled thymidine into DNA increased 620 and 1,880% after 2 and 3 days in culture, respectively, as the cells assumed a more flattened phenotype. Although cells on M6 did not divide, both basal rates of thymidine labeling and sensitivity to serum modulators of DNA synthesis were enhanced by the M6 surface, as compared with plastic. Culture of type II cells on surfaces of purified fibronectin enhanced the rate of DNA synthesis in a manner similar to that observed on M6; this effect was blocked by antifibronectin. The data suggest that more rapid fibronectin synthesis and deposition are important components of the response of type II cells to primary culture. Extracellular matrix produced by type II cells appears to be similar to the basement membrane onto which these cells proliferate in vivo after lung injury. A fibronectin-rich surface in itself may thus induce additional extracellular matrix synthesis and further direct cellular differentiation and proliferation.

Animals↗
PubMed2003

Fibronectin matrix polymerization regulates small airway epithelial cell migration.

The continuous conversion of soluble fibronectin into extracellular matrix fibrils occurs through a dynamic, cell-dependent process. As the extracellular matrix is assembled, changes in the conformation of matrix proteins may expose biologically active, matricryptic sites that alter cell behavior. In this study, an in vitro model of wound healing was used to determine the role of matrix fibronectin in airway epithelial cell motility. Our findings indicate that, under basal conditions, small airway epithelial cell (SAEC) migration requires active fibronectin matrix polymerization. Furthermore, SAEC migration is increased significantly by the interaction of cells with a recombinant construct containing fibronectin's matricryptic III-1 site. In contrast, addition of increasing amounts of fibronectin to SAECs significantly decreased the rate of cell migration. This fibronectin-induced inhibition of cell migration was overcome by blocking excess fibronectin matrix deposition. These data indicate that SAEC migration is regulated in a biphasic manner by the polymerization of fibronectin in the extracellular matrix and suggest a stimulatory role for fibronectin's matricryptic III-1 site in cell motility.

Animals↗
PubMed1980

Ultrastructural studies on the origin and structure of matrix vesicles in bone of young rats.

Tibiae of young rats were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in order to study the origin and structure of matrix vesicles in periosteal bone. SEM studies have shown that periosteal osteoblasts have elongated processes with globular structures of 0.1 micron in diameter attached to the cell surface and processes. Similar structures were found to cover the inner surface of osteoblastic lacunae. The SEM studies have further shown that in the periosteal surface (forming bone) the above-described globules once mineralized, aggregated to form larger, nonhomogeneous mineralized spherules in which, by proper treatment with NaOCl, hydroxyapatite crystals could be exposed. Endosteal osteoblasts had fewer processes, devoid of the globular structures. Similarly, osteocytic and osteoclastic processes, although elongated and numberous, were not covered by the globular structures. In the matrix, collagen fibers of forming bone were randomly orientated, while in the deeper areas of bone they formed bundles with a longitudinal orientation. TEM studies have shown that the structures found on the osteoblastic surface and in the matrix are membrane-bound matrix vesicles which seem to be formed by budding from cell processes. Preformed membrane-bound vesicles were also observed by TEM inside sections of osteoblastic processes. These vesicles resembled the extracellular matrix vesicles in size and shape, thus giving the impression that at least some of the matrix vesicles are preformed cellular structures. While comparing SEM with TEM, it can be conducted that in bone, as in cartilage, matrix vesicles which probably serve as the initial locus of calcification, are formed directly by osteoblasts.

Animals↗
PubMed1997

Role of matrix metalloproteinases and their inhibitors in pancreatic cancer.

BACKGROUND/AIMS: The matrix metalloproteinases are a family of proteolytic enzymes which normally have an important physiological role in tissue remodelling and wound healing, but more recently have been implicated in the proteolytic events which occur during tumour invasion. METHODS: The expanding family of matrix metalloproteinases and the specific tissue inhibitors of the matrix metalloproteinases are reviewed including their classification, structure, function, regulation of activity, and tissue expression with particular reference to pancreatic cancer. The effect of synthetic matrix metalloproteinases inhibitors in preclinical studies is reviewed together with the results of ongoing clinical trials in pancreatic cancer. RESULTS: Pancreatic cancer is associated with the overexpression of several matrix metalloproteinases with a reduced expression of their specific inhibitors. Orally bioavailable matrix metalloproteinase inhibitors have successfully completed phase I/II clinical trials with promising results. Multicentre randomised controlled phase IIb/III clinical trials aren currently under way in pancreatic cancer. CONCLUSIONS: Matrix metalloproteinase inhibition may represent a novel approach to the management of pancreatic cancer not only in advanced disease, but in the adjuvant treatment setting following tumour resection either alone or in combination with existing chemotherapeutic agents.

Clinical Trials as Topic↗
PubMed1995

Human endothelial cell damage by neutrophil-derived cathepsin G. Role of cytoskeleton rearrangement and matrix-bound plasminogen activator inhibitor-1.

Cathepsin G, a major protease released by activated neutrophils, induces functional and morphological damage to human endothelial cells. We studied the mechanisms involved and ways to reverse this damage. Cathepsin G induced a concentration- and time-dependent injury to human umbilical vein endothelial cell (HUVEC) morphology simultaneous with cytoskeleton rearrangement. Preincubation of the endothelial monolayer with phallacidin completely prevented damage to cell morphology by cathepsin g, whereas preincubation with cytochalasin b potentiated its activity. Damage to cell shape and F-actin cytoskeleton were prevented by eglin C, and inhibitor of the active site of cathepsin G. Furthermore, cathepsin G increased transcellular permeability to albumin and induced a time-dependent detachment of PAI-1 from the extracellular matrix of a cell-free system. The inhibition of matrix-bound PAI-1 activity by specific antibodies induced matrix-bound PAI-1 activity by specific antibodies induced changes in HUVEC monolayers similar to those observed after cathepsin G. However, although stabilization of F-actin microfilaments by phallacidin prevented changes in cell shape, it did not prevent the ability of cathepsin G to increase cell permeability and release matrix PAI-1. The damage of cathepsin G to cell morphology and cytoskeleton arrangement was reversed within 12 hours if the deendothelialization area was < 50% to 55% and the subendothelial matrix was still able to bind the newly synthesized PAI-1. Thrombin, whose role in the thrombotic process is well known, also induced changes in cell morphology and cytoskeleton arrangement of HUVEC. Cathepsin G reaches the subendothelial matrix through an increase in cell permeability and injures endothelial cell morphology by detaching matrix-bound PAI-1. These events expose a highly thrombogenic surface to which platelets can adhere, become activated, attract further neutrophils, and trigger thrombus formation.

Cathepsin G↗
PubMed2002

Intracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion injury.

BACKGROUND: Matrix metalloproteinases are best recognized for their ability to degrade the extracellular matrix in both physiological and pathological conditions. However, recent findings indicate that some of them are also involved in mediating acute processes such as platelet aggregation and vascular tone. The acute contractile defect of the heart after ischemia-reperfusion may involve the proteolytic degradation of the thin filament protein troponin I; however, the protease responsible for this remains obscure. METHODS AND RESULTS: Here we report that matrix metalloproteinase-2 is colocalized with troponin I within the thin myofilaments of cardiomyocytes in ischemic-reperfused hearts and that troponin I is a novel intracellular target for proteolytic cleavage by matrix metalloproteinase-2. Inhibition of matrix metalloproteinase-2 activity prevented ischemia-reperfusion-induced troponin I degradation and improved the recovery of mechanical function of the heart. CONCLUSIONS: These data reveal for the first time a novel molecular mechanism by which matrix metalloproteinase-2 causes acute myocardial dysfunction after ischemia-reperfusion-injury and that matrix metalloproteinase-2 has a biological action within the cell.

Actin Cytoskeleton↗
PubMed1998

Expression of extracellular matrix proteins accompanies lesion growth in a model of intimal reinjury.

Reinjury of rat arterial lesions induces an increase in lesion size that is not associated with an increase in cell number. In this study, matrix volume was examined after reinjury to preexisting lesions, and the kinetics of matrix gene expression and activity of proteolytic enzymes in the lesion were evaluated. Volume densitometry in intima showed a significant increase in matrix volume 28 days after the reinjury, although no change was observed at 14 days. Three common vascular matrix molecules, alpha1(I)procollagen, tropoelastin, and fibronectin, were expressed highly at 7 days after the reinjury. Expression of tropoelastin remained upregulated for the entire 28 days after the reinjury, whereas alpha1(I)procollagen and fibronectin returned to the control level by 28 days. Protease activity was also increased after reinjury. Within days, a marked increase in urokinase plasminogen activator activity was observed in intima, and this activity decreased to control level by 14 days. The activity of tissue plasminogen activator did not change. The 95-kDa gelatinolytic activity was increased 1 to 2 days after the reinjury, but no change in other gelatinolytic activities was observed. These findings demonstrate that the accumulation of extracellular matrix is important in the increase in lesion size after reinjury and that a balance of matrix synthesis and degradation may explain why no change in matrix volume was detected until 28 days after the reinjury.

Animals↗
PubMed2006

Cell-matrix contact prevents recognition and damage of endothelial cells in states of heightened immunity.

BACKGROUND: Autoimmunity may exacerbate vascular disease, particularly in the form of anti-endothelial cell (EC) antibodies. The increased morbidity of cardiovascular diseases in concert with diabetes mellitus, hypertension, and other systemic illnesses may reflect the increase presence and potency of these antibodies. Matrix-embedded ECs act as powerful regulators of vascular repair accompanied by significant reduction in expected systemic and local inflammation. We compared the immune response against free and matrix-embedded ECs in naïve mice and mice with heightened EC immune reactivity. METHODS AND RESULTS: Mice were presensitized to EC with repeated (days 0, 21, 35) subcutaneous injections of saline-suspended porcine EC (PAE) (5 x 10(5) cells). Controls received saline injections. On day 42, mice received 5 x 10(5) matrix-embedded or free PAEs. Circulating PAE-specific antibodies and effector T-cells were analyzed via flow cytometry, and xenoreactive lymphocytes via ELISPOT, 90 days after implantation. PAE-specific antibody-titers, frequency of CD4+-effector cells, and xenoreactive splenocytes were 2- to 4-fold lower (P<0.0001) when naïve mice were injected with matrix-embedded instead of saline-suspended PAEs. Though basal levels of circulating antibodies were significantly elevated after serial PAE injections (2210+/-341 mean fluorescence intensity, day 42) and almost doubled again 90 days after injection of a fourth set of free PAEs, antibody levels declined by half in recipients of matrix-embedded PAEs at day 42 (P<0.0001). Levels of CD4+-effector cells and xenoreactive splenocytes showed similar results. CONCLUSIONS: Implantation of free PAE elicits a significant immune response in naïve mice and even more pronounced in mice with predeveloped anti-endothelial immunity. Matrix-embedding protects xenogeneic ECs against immune reaction in naïve mice and to a similar extent in mice with heightened immune reactivity. Matrix-embedded EC might offer a promising approach for treatment of advanced cardiovascular disease.

Animals↗
PubMed1987

Plasminogen activator inhibitor is associated with the extracellular matrix of cultured bovine smooth muscle cells.

The extracellular matrix secreted by cultured bovine smooth muscle cells (BSMC) contains an endothelial type plasminogen activator (PA) inhibitor. When PA is incubated with the matrix, a high molecular weight complex containing a truncated PA inhibitor is released into the supernatant. The inhibitor also dissociates from the matrix by treatment with glycine, pH 2.7, in its intact, functionally active, 45-kD form, whereas treatment of the matrix with thrombin results in the release of a cleaved, inactive, 41 kD PA inhibitor. Bowes melanoma cells but not smooth muscle cells cultured on BSMC matrices decrease available matrix associated PA inhibitor. PA inhibitor incorporated into the extracellular matrix may serve an important role in the regulation of plasminogen activator mediated matrix degradation.

Animals↗
PubMed2002

Latrunculin and cytochalasin decrease chondrocyte matrix retention.

The proteoglycan-rich extracellular matrix (ECM) directly associated with the cells of articular cartilage is anchored to the chondrocyte plasma membrane via interaction with the hyaluronan receptor CD44. The cytoplasmic tail of CD44 interacts with the cortical cytoskeleton. The objective of this study was to determine the role of the actin cytoskeleton in CD44-mediated matrix assembly by chondrocytes and cartilage matrix retention and homeostasis. Adult bovine articular cartilage tissue slices and isolated chondrocytes were treated with latrunculin or cytochalasin. Tissues were processed for histology and chondrocytes were examined for CD44 expression and pericellular matrix assembly. Treatments that disrupt the actin cytoskeleton reduced chondrocyte pericellular matrix assembly and the retention of proteoglycan within cartilage explants. There was enhanced detection of a neoepitope resulting from proteolysis of aggrecan. Cytoskeletal disruption did not reduce CD44 expression, as monitored by flow cytometry, but detergent extraction of CD44 was enhanced and hyaluronan binding was decreased. Thus, disruption of the cytoskeleton reduces the anchorage of CD44 in the chondrocyte membrane and the capacity of CD44 to bind its ligand. The results suggest that cytoskeletal disruption within cartilage uncouples chondrocytes from the matrix, resulting in altered metabolism and deleterious changes in matrix structure.

Animals↗