The growth kinetics of subcultured human synovial fibroblasts from 16 patients with inflammatory and noninflammatory arthropathies were studied in antibiotic free media. The experimental design allowed a clear distinction between the growth rates and final saturation densities achieved. The effects of refeeding and of the serum concentration were evaluated for each line. Inflammatory lines achieved significantly higher final saturation densities and growth rates than noninflammatory lines for most protocols, but the differences between rheumatoid and nonrheumatoid groups were less marked. Inflammatory fibroblasts demonstrated a greater independence to nutritional and growth stimulatory factors in their microenvironment than noninflammatory fibroblasts.The modulation of fibroblastic proliferation in culture is under complex control, and many of the factors involved are incompletely understood (1). Nevertheless, untransformed fibroblastic cells often exhibit
greater or lesser degrees of density-dependent inhibition of growth (DDI). One measurement of DDI is reflected by the final cell saturation density (FSD) achieved by the fibroblastic cells under defined conditions of refeeding the cultures and of serum supplementation (2,3).The precise mechanisms involved in DDI are uncertain, but one possibility is that it is effected by the actual contact between cells. A mechanism for this contact inhibition of growth based on mutual modification of surface carbohydrate moieties by surface glycosyltransferases (4) has received both considerable support (5,6) and criticism (7,8).However, the FSD achieved by fibroblastic cells can be affected by different sets of circumstances in the microenvironment of the culture other than those affecting the growth rate of the cells. For example, the authors had previously demonstrated that although a change in culture pH of human skin fibroblasts does not affect growth rates, the FSD at the higher pH values was always greater than that achieved at lower pH at any serum concentration between 1% and 20% (9). Nutritional effects, operative mainly through diffusion gradients of the larger molecules in the extracellular microenvironment (3,10), may also modulate DDI under certain circumstances. However, we have demonstrated that such diffusion effects cannot entirely account for the phenomenon of DDI under various conditions of nutrient availability and serum supplementation (10).Previously published work on the growth of human rheumatoid and nonrheumatoid synovial cells in
