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Microfilament Modification by Dihydrocytochalasin B Causes Retinoic Acid-Modulated Chondrocytes to Reexpress the Differentiated Collagen Phenotype without a Change in Shape

Paul D. Benya, Peter D. Brown and Silvia R. Padilla
The Journal of Cell Biology
Vol. 106, No. 1 (Jan., 1988), pp. 161-170
Stable URL: http://www.jstor.org/stable/1612792
Page Count: 10
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Microfilament Modification by Dihydrocytochalasin B Causes Retinoic Acid-Modulated Chondrocytes to Reexpress the Differentiated Collagen Phenotype without a Change in Shape
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Abstract

Primary monolayers of rabbit articular chondrocytes synthesize high levels of type II collagen and proteoglycan. This capacity was used as a marker for the expression of the differentiated phenotype. Such cells were treated with 1 μg/ml retinoic acid (RA) for 10 d to produce a modulated collagen phenotype devoid of type II and consisting of predominantly type I trimer and type III collagen. After transfer to secondary culture in the presence of RA, the stability of the RA-modulated phenotype was investigated by culture in the absence of RA. Little reexpression of type II collagen synthesis occurred in this period unless cultures were treated with 3 × 10-6 M dihydrocytochalasin B to modify microfilament structures. Reexpression of the differentiated phenotype began between days 6-8 and was essentially complete by day 14. Substantial reexpression occurred by day 8 without a detectable increase in cell rounding. Colony formation, characteristic of primary chondrocytes, was infrequent even after reexpression was complete. These data suggest that the integrity of microfilament cytoskeletal structures can be a source of regulatory signals that mechanistically appear to be more proximal to phenotypic change than the overt changes in cell shape that accompany reexpression of subculture-modulated chondrocytes in agarose culture (Benya, P. D., and J. D. Shaffer, 1982. Cell. 30:215-224).

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