Density-dependent regulation of skin-fibroblast glycosaminoglycans in vitro: control by a secreted factor.

Glycosaminoglycans (GAG) secretion by human skin fibroblasts in monolayer culture was inversely proportional to cell density, the relationship applying both within and between cultures of different fibroblast lines. There was neither substantial extracellular degradation nor significant endocytosis of the GAG from the culture medium. The mechanism controlling the inhibition of secretion did not involve the exhaustion of serum in the culture medium, a decline in cell viability or a negative feedback related to hyaluronic-acid concentration, and did not require intercellular contact. The inhibitory factor could be transferred from one culture to another and appeared to be secreted by the fibroblasts concomitantly with the GAG. The effect of cell density on GAG must be considered in future studies of drugs in vitro or other manipulations of the cellular environment.