Warren Knudson

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The macrophage migration inhibitory factor (MIF) receptor (CD74) was cloned recently, but the signaling mechanism is not evident. We hypothesized that signaling requires an additional molecule such as CD44, which activates nonreceptor tyrosine kinases. We utilized the CD74- and CD44-deficient COS-7/M6 cell to create stable transfectants expressing CD74,(More)
The predominant proteoglycan present in cartilage is the large chondroitin sulfate proteoglycan 'aggrecan'. Following its secretion, aggrecan self-assembles into a supramolecular structure with as many as 50 monomers bound to a filament of hyaluronan. Aggrecan serves a direct, primary role providing the osmotic resistance necessary for cartilage to resist(More)
The high molecular weight glycosaminoglycan hyaluronan plays an important role in tissue remodeling during development, normal tissue homeostasis, and disease. The interaction of hyaluronan with matrix hyaluronan-binding proteins and cell-surface hyaluronan receptors regulates many aspects of cell behavior such as cell migration, cell-cell adhesion, and(More)
Hyaluronan exerts a variety of biological effects on cells including changes in cell migration, proliferation, and matrix metabolism. However, the signaling pathways associated with the action of hyaluronan on cells have not been clearly defined. In some cells, signaling is induced by the loss of cell-hyaluronan interactions. The goal of this study was to(More)
Bone morphogenetic protein 7 (BMP-7) regulates cellular metabolism in embryonic and adult tissues. Signal transduction occurs through the activation of intracellular Smad proteins. In this paper, using a yeast two-hybrid screen, Smad1 was found to interact with the cytoplasmic domain of CD44, a receptor for the extracellular matrix macromolecule hyaluronan.(More)
Articular chondrocytes express the matrix receptors CD44 and integrins. Both of these receptors exhibit interactions with adjacent extracellular matrix macromolecules. In addition, both integrins and CD44 have the capacity for signal transduction as well as modulated interactions with the actin cytoskeleton. As such, both receptor families provide the(More)
Hyaluronan turnover occurs systemically from the lymph and serum as well as locally by the same cells responsible for its synthesis. Local turnover involves receptor-mediated uptake and delivery to lysosomes. Of the many hyaluronan binding proteins/receptors known, the participation of CD44 in the internalization of hyaluronan has been best characterized.(More)
Bovine articular chondrocytes cultured in alginate beads were used to study the effect of catabolic cellular mediators on CD44 expression. Treatment with either the 29-kDa fragment of fibronectin or interleukin-1 alpha results in a time- and dose-dependent inhibition of proteoglycan synthesis as well as a stimulation in the expression of CD44 mRNA level as(More)
Respiratory syncytial virus (RSV) is an important human respiratory pathogen, particularly in infants. Glycosaminoglycans (GAGs) have been implicated in the initiation of RSV infection of cultured cells, but it is not clear what type of GAGs and GAG components are involved, whether the important GAGs are on the virus or the cell, or what the magnitude is of(More)
A recently developed non-ionic surfactant called Solutol HS 15 (poly-oxyethylene esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells. At a concentration of(More)