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Restoration of the Differentiated Functions of Serially Passaged Chondrocytes Using Staurosporine
Laurence Borge, Francois Lemare, Sylvie Demignot and Monique Adolphe
In Vitro Cellular & Developmental Biology. Animal
Vol. 33, No. 9 (Oct., 1997), pp. 703-709
Published by: Society for In Vitro Biology
Stable URL: http://www.jstor.org/stable/4294678
Page Count: 7
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Among the various directions explored in order to have a large number of differentiated articular chondrocytes easily available, the restoration of the differentiated properties after cell multiplication in monolayer has been proposed. It has been clearly shown that the synthesis of cartilage proteoglycans and type II collagen synthesis is coincident with the presence of a faint microfibrillar architecture but is absent in chondrocytes showing well-defined actin cables. Staurosporin, mainly described as a protein kinase C inhibitor, has also been shown to rapidly induce the disruption of the actin microfilaments. The purpose of this paper was to investigate whether properties of differentiated chondrocytes were reinitiated upon staurosporin treatment of serially passaged chondrocytes. Results showed, after staurosporine treatment of cells at Passage two for 5 d, complete suppression of type I and type III collagen synthesis and induction of type II collagen synthesis and of Alcian blue stainable matrix. Additionally, we showed that staurosporin restored metabolic responses that chondrocytes in primary culture exhibit upon interleukin-lβ treatment (decrease of Alcian blue-positive cells, induction of expression of the 92 kDa gelatinase, nitric oxide production). We conclude that staurosporin is a potent redifferentiating agent of articular chondrocytes that have been subcultured up to Passage two for multiplication. Taking into account that the cellularity of cartilage is very low, staurosporine-treated chondrocytes could be useful as an alternative cellular model to evaluate pharmacotoxicological effects of drugs.
In Vitro Cellular & Developmental Biology. Animal © 1997 Society for In Vitro Biology