Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis

“…It is well known that chondrocytes can adopt different phenotypes, including those associated with the growth plate (resting, proliferating, hypertrophic), those associated with the different zones of AC, and the dedifferentiated phenotype observed in monolayer culture (3,7,13,17). Numerous studies have investigated the phenotypic alterations observed in OA cartilage at the molecular level by RT-PCR, Northern and in situ hybridizations, and immunohistologic analyses.…”

“…These changes in the biosynthetic profile of dedifferentiated chondrocytes resemble some of the phenotypic changes displayed by OA chondrocytes, and the matrix they produce is similar to that synthesized by chondroprogenitor cells (7)(8)(9)(10)(11)(12)(13)17,(37)(38)(39)(40). However, the mechanisms responsible for the phenotypic instability of chondrocytes and the regulation of these different chondrocyte-specific phenotypes remain poorly understood.…”

“…The chondro-cyte response may lead, in certain situations, to longterm changes in the phenotype of the cell, and therefore to an inability to properly repair or maintain the cartilage ECM (4). This is exemplified by the phenotypic changes in the patterns of production or in the temporal or spatial distribution of the synthesis of interstitial collagens, fibroblast-type proteoglycans, and production of ECM proteins associated with fetal development that occur during the development of osteoarthritis (OA), dedifferentiation in culture, or in response to certain types of cartilage injury (6)(7)(8)(9)(10)(11)(12)(13).…”

“…Studies that have examined the plasticity of the chondrocyte phenotype from many different species have consistently shown that culture of these cells in monolayers on plastic substrata for prolonged periods or upon repeated passages leads to the loss of their spherical shape and to the acquisition of an elongated fibroblast-like morphology (7,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). These morphologic alterations are accompanied by profound biochemical changes, including loss of the cartilage-specific phenotype, as evidenced by an arrest of the synthesis of the cartilage-specific collagens (types II, IX, and XI) and proteoglycans (aggrecan), initiation of synthesis of the interstitial collagens (types I, III, and V), and increase in the synthesis of fibroblasttype proteoglycans (versican) at the expense of aggrecan (7,17,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

In vitro synthesis and degradation of collagen by chick chondrocytes and fibroblasts

“…When these cells are kept in monolayer culture for several weeks, they change morphology from a polygonal to an elongated shape. They stop producing cartilage type II collagen and switch to synthesis of other types of collagen, mainly type I collagen, which is a major product of fibrobtasts [1][2][3][4]. This process is more rapid when chondrocytes are maintained in the presence of 5-bromodeoxyuridine [5] or calvaria conditioned medium [6] or fibronectin [7].…”