Production of and response to growth-stimulating activity in isolated bone cells

Autologous growth-promoting activity has been shown to be secreted by bone organ cultures. To identify the cellular source of these growth factors, we have studied the activity present in cell extracts prepared from isolated bone cells released early or late from mouse calvariae following collagenase digestion. Previous studies have established that early released cell populations reside on the bone surface and consist of a heterogeneous mixture of cells that are less osteoblastic than late released cells. We find that soluble extracts of the latter cells contain more growth-promoting activity/mg of cellular protein than those of the former. By this criterion late released cells appear to be the major source of endogenous growth factors. On the other hand, upon exposure to bone cell-derived cell extracts, early released cells express a greater-fold increase in [3H]thymidine incorporation into acid insoluble radioactivity than late released osteoblasts because of the high basal mitogenic activity of the latter which may be related to their production of autologous growth factor. These data suggest that both early and later released cells may be major targets for bone growth factors produced in situ by late released osteoblasts.