The chondrocyte pericellular matrix: a model for hyaluronan-mediated cell-matrix interactions

Knudson, Cheryl B.; Nofal, Ghada A.; Pamintuan, L.; Aguiar, Dean J.

doi:10.1042/bst0270142

Cited by 71 publications

(37 citation statements)

References 21 publications

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“…In this study, we demonstrate that cell-based catabolism of aggrecan does occur after 5 days of culture, resulting in the expression of both G1-DIPEN and G1-ITEGE fragments retained within the cellassociated matrix of chondrocytes in alginate beads (Figures 2A, 2F, 2G, 3A, and 3C). This implies that, under these culture conditions, the chondrocytes have not only synthesized sufficient aggrecan to reestablish a cell-associated matrix (28), but have also begun maintenance turnover of this proteoglycan by ADAMTS proteinases, as well as by MMPs.…”

Section: Discussionmentioning

confidence: 99%

The accumulation of intracellular ITEGE and DIPEN neoepitopes in bovine articular chondrocytes is mediated by CD44 internalization of hyaluronan

Flory¹,

Fosang²,

Knudson³

2006

Arthritis & Rheumatism

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Objective. A dramatic loss of aggrecan proteoglycan from cartilage is associated with osteoarthritis. The fate of residual G1 domains of aggrecan is unknown, but inefficient turnover of these domains may impede subsequent repair and retention of newly synthesized aggrecan. Thus, the objective of this study was to determine whether ITEGE-and DIPEN-containing G1 domains, generated in situ, are internalized by articular chondrocytes, and whether these events are dependent on hyaluronan (HA) and its receptor, CD44.Methods. ITEGE and DIPEN neoepitopes were detected by immunofluorescence staining of bovine articular cartilage chondrocytes treated with or without interleukin-1␣ (IL-1␣). Additionally, purified ITEGEor DIPEN-containing G1 domains were aggregated with HA and then added to articular chondrocytes, articular chondrocytes transfected with CD44‚67, or COS-7 cells transfected with or without full-length CD44. Internalized epitopes were distinguished by their resistance to extensive trypsinization of the cell surface.Results. Both ITEGE and DIPEN were visualized within the extracellular cell-associated matrix of chondrocytes as well as within intracellular vesicles. Following trypsinization, the intracellular accumulation of both epitopes was clearly visible. IL-1 treatment increased extracellular as well as intracellular ITEGE epitope accumulation. Once internalized, the ITEGE neoepitope became localized within the nucleus and displayed little colocalization with HA, DIPEN, or other G1 domain epitopes. The internalization of both ITEGE and DIPEN G1 domains was dependent on the presence of HA and CD44.Conclusion. One important mechanism for the elimination of residual G1 domains following extracellular degradation of aggrecan is CD44-mediated cointernalization with HA.

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Section: Discussionmentioning

confidence: 99%

The accumulation of intracellular ITEGE and DIPEN neoepitopes in bovine articular chondrocytes is mediated by CD44 internalization of hyaluronan

Flory¹,

Fosang²,

Knudson³

2006

Arthritis & Rheumatism

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“…Studies in our laboratory have demonstrated that binding to CD44 is the primary means of retention and anchoring proteoglycan aggregates to the surface of chondrocytes. [20][21][22] In addition, CD44 also participates in the internalization and turnover of HA in articular chondrocytes as well as other cells. 58,59 Disruption of CD44 function may disturb cartilage homeostasis, leading to pathological changes and loss of extracellular matrix such as observed in degenerative diseases.…”

Section: Osteoarthritismentioning

confidence: 99%

“…However, our studies have demonstrated that the binding of hyaluronan to the cell surface receptor CD44 allows the retention of a subpopulation of aggrecan in the pericellular matrix of the chondrocytes (Figure 1). [20][21][22] Thus CD44, hyaluronan and aggrecan comprise important elements for pericellular matrix assembly and maintenance of matrix homeostasis. Disruption of native hyaluronan-cell interactions with hyaluronan hexasaccharides resulted in a delay in the formation of condensations as well as a delay in the deposition of type II collagen and aggrecan.…”

Section: Aggrecanmentioning

confidence: 99%

Cartilage proteoglycans

Knudson

2001

Seminars in Cell & Developmental Biology

547

412

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“…Also, hyaluronan mediates assembly of complex pericellular matrices containing several components. 5,18,19 Although the latter can be reconstituted in part by the addition of exogenous components, 19,20 it is unlikely that the complete native configuration of these matrices can be duplicated in this way. In the present study we examine the effects of perturbing endogenous hyaluronan-cell interactions on glioma cell growth and invasion, using two different approaches.…”

mentioning

confidence: 99%

Perturbation of Hyaluronan Interactions Inhibits Malignant Properties of Glioma Cells

Ward

Huang

Guo

et al. 2003

The American Journal of Pathology

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Malignant progression of gliomas is characterized by acquisition of inappropriate growth and invasive properties. In vitro, these malignant properties are reflected in, and measured by, the ability to grow in an anchorage-independent manner and to invade artificial extracellular matrices. The results of numerous studies have suggested that the extracellular and pericellular matrix polysaccharide, hyaluronan, plays an important role in these attributes of malignant cancer cells. However, with respect to glioma cells, most studies have addressed the effect of exogenously added hyaluronan rather than the function of endogenous tumor cell-associated hyaluronan. In this study we manipulate hyaluronan-glioma cell interactions by two methods. The first is administration of small hyaluronan oligosaccharides that compete for endogenous hyaluronan polymer interactions, resulting in attenuation of hyaluronan-induced signaling. The second is overexpression of soluble hyaluronanbinding proteins that act as a competitive sink for interaction with endogenous hyaluronan, again leading to attenuated signaling. We find that both treatments inhibit anchorage-independent growth, as measured by colony formation in soft agar, and invasiveness, as measured by penetration of reconstituted basement membrane matrices. Based on our findings, we conclude that endogenous hyaluronan interactions are essential for these two fundamental malignant properties of glioma cells. Malignant forms of glioblastoma rarely metastasize to distant sites but they are highly proliferative and invasive tumors that destroy normal brain structure and result in high morbidity. As with many types of cancers, up-regulation of growth factor pathways and loss of tumor suppressors have been implicated in glioma development but the mechanisms underlying progression of gliomas to malignancy are by no means established. 1 It has become increasingly apparent that cooperation between signaling pathways induced by growth factors and cytokines and those induced by cell-cell and cell-extracellular matrix interactions are central to regulation of cell behavior. Recent work has highlighted the importance of altered cell-matrix interactions in the acquisition of malignant characteristics. [2][3][4] Hyaluronan is a very large, negatively charged polysaccharide composed of repeating units of glucuronic acid and N-acetylglucosamine. It is ubiquitously associated with extracellular and pericellular matrices but is especially enriched around proliferating and migrating cells. 5 Interactions of hyaluronan with a variety of cell-surface receptors activate intracellular signaling pathways that regulate various aspects of cell behavior 6 and, in tumor cells, promote malignant characteristics. [7][8][9] Several studies have provided evidence that hyaluronan-cell interactions may play a role in glioma invasiveness. For example, addition of exogenous hyaluronan enhances glioma cell migration and invasion in vitro, and this effect is blocked by antibodies or anti-sense oligonucleotides to C...

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The chondrocyte pericellular matrix: a model for hyaluronan-mediated cell-matrix interactions

Cited by 71 publications

References 21 publications

The accumulation of intracellular ITEGE and DIPEN neoepitopes in bovine articular chondrocytes is mediated by CD44 internalization of hyaluronan

The accumulation of intracellular ITEGE and DIPEN neoepitopes in bovine articular chondrocytes is mediated by CD44 internalization of hyaluronan

Cartilage proteoglycans

Perturbation of Hyaluronan Interactions Inhibits Malignant Properties of Glioma Cells

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