title: Adhesion-mediated signal transduction in human articular chondrocytes: the influence of biomaterial chemistry and tenascin-C.
abstract: Chondrocyte 'dedifferentiation' involves the switching of the cell phenotype to one that no longer secretes extracellular matrix found in normal cartilage and occurs frequently during chondrocyte expansion in culture. It is also characterized by the differential expression of receptors and intracellular proteins that are involved in signal transduction pathways, including those associated with cell shape and actin microfilament organization. The objective of this study was to examine the modulation of chondrocyte phenotype by cultivation on polymer substrates containing poly(ethylene glycol) (PEG). We observed differential arrangement of actin organization in articular chondrocytes, depending on PEG length. When cultivated on 300 g/mol PEG substrates at day 19, chondrocytes had lost intracellular markers characteristic of the differentiated phenotype, including type II collagen and protein kinase C (PKC). On these surfaces, chondrocytes also expressed focal adhesion and signaling proteins indicative of cell attachment, spreading, and FA turnover, including RhoA, focal adhesion kinase, and vinculin. The switch to a dedifferentiated chondrocyte phenotype correlated with integrin expression. Conversely, the expression of CD44 receptors coincided with chondrogenic characteristics, suggesting that binding via these receptors could play a role in maintaining the differentiated phenotype on such substrates. These effects can be similar to those of compounds that interfere in intracellular signaling pathways and can be utilized to engineer cellular response.
authors.affiliation: IsoTis SA, Prof. Bronkhorstlaan 10, 3723 MB Bilthoven, The Netherlands. tmahmood@amgen.com
authors.forename: Tahir A
authors.initials: TA
authors.lastname: Mahmood
authors.forename: Ruben
authors.initials: R
authors.lastname: de Jong
authors.forename: Jens
authors.initials: J
authors.lastname: Riesle
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Clemens A
authors.initials: CA
authors.lastname: van Blitterswijk
mesh_terms: D000199:Actins / Q000378:metabolism; D001672:Biocompatible Materials / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology; D002448:Cell Adhesion / Q000502:physiology*; D018929:Cell Culture Techniques; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects; D022001:Focal Adhesions / Q000187:drug effects; D006801:Humans; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D019063:Tenascin / Q000494:pharmacology*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors
chemical_list: D000199:Actins; D001672:Biocompatible Materials; D019063:Tenascin; D011092:Polyethylene Glycols; D020742:rhoA GTP-Binding Protein