beta(1)-Integrin-collagen interaction reduces chondrocyte apoptosis

We have observed that the spent culture media in suspended chondrocyte cult ures is essential for the survival of the cells, since complete change of t he spent media induces severe programmed cell death (apoptosis). Moreover, we showed that extracellular matrix (ECM) molecules in the culture media pr ovide vital chondrocyte-matrix interactions; when media are changed, cells are deprived of matrix molecules and undergo apoptosis. In this paper we re port that interaction with collagen, a ubiquitous extracellular matrix mole cule, is essential for chondrocyte Survival. Such an interaction causes cho ndrocyte aggregation and reduces the level of chondrocyte apoptosis, Hyalur onan,: an abundant ECM molecule, can influence the effects of collagen by p reventing chondrocyte aggregation. Degradation of hyaluronan with hyaluroni dase results in chondrocyte aggregation, and this reduces the level of chon drocyte apoptosis. Experiments with an antibody to integrin beta(1) suggest that the collagen-chondrocyte interactions are mediated through integrin b eta(1), and these interactions may protect chondrocytes from apoptosis. We hypothesize that hyaluronan binds aggrecan and link protein, forming stable ternary complexes, which interact with the chondrocyte surface, perhaps vi a CD44, and thus maintains a stable chondrocyte-matrix network. (C) 1999 El sevier Science B.V./International Society of Matrix Biology. All rights res erved.