Production of collagens, collagenase and collagenase inhibitor during the dedifferentiation of articular chondrocytes by serial subcultures.

Rabbit articular chondrocytes were cultured in monolayer and the progressive loss of their differentiated phenotype was monitored from passage to passage. The cell densities achieved in confluent cultures decreased abruptly between the primoculture and the second or third subculture, and more slowly thereafter, reflecting parallel morphological changes. The synthesis of collagen (but not that of other proteins) decreased sharply, and a smaller proportion of collagen was incorporated into the matrix. Cells in primoculture synthesized mainly the cartilage-specific collagens, types II and XI, which were mostly deposited in the matrix, but no type I nor III collagen. With increasing passages, the synthesis of type II collagen decreased progressively while that of types I and III collagens increased, the latter being almost completely released in the culture medium. Simultaneously, the production of type XI collagen was apparently switched to that of type V. Fully differentiated confluent chondrocytes in primoculture produced the collagenase inhibitor TIMP (tissue inhibitor of metalloproteinases) but no detectable procollagenase; their production of procollagenase was, however, induced by interleukin 1. The production of TIMP increased from passage to passage. A spontaneous production of procollagenase was only occasionally observed in confluent cultures of dedifferentiated chondrocytes. However, interleukin 1 induced an always higher production of procollagenase from dedifferentiated chondrocytes than from cells in primoculture.