Effects of transforming growth factor type beta upon bone cell populations grown either in monolayer or semisolid...

Bone has been shown to store large amounts of transforming growth factor type beta (TGF beta) and this has recently been found to be synthesized by bone-forming cells. We report on studies undertaken to examine the effects of platelet-derived TGF beta on different bone cell populations, isolated from 1-day postnatal rat calvaria by sequential enzymatic digestion. In addition, we tried to determine which of these cell populations synthesize TGF beta. In this regard, evidence was collected to indicate that cell populations which were shown to be enriched with osteoblast-like cells synthesize TGF beta. Although the production of the factor appeared to be limited to a particular cell type, its action was found to be of a more general character, as all cell populations were found to respond to TGF beta. Contrary to earlier reports, TGF beta was shown to be inhibitory upon cell proliferation. In this context, growth of cells released during early digestions was reduced considerably more than growth of those released during late digestions. Studies on the effect upon protein synthesis revealed that TGF beta specifically inhibited collagen but not the synthesis of noncollagenous proteins. The synthesis of collagen was altered to a greater extent in cells isolated during late digestions than in cells of the early populations. Further information on the TGF beta-mediated effects on bone cell biology was provided by data showing that both alkaline phosphatase and cAMP production in response to PTH was greatly reduced by TGF beta. Finally, experiments performed to determine whether TGF beta induces any of the bone cell populations to acquire the transformed phenotype revealed that only populations previously shown to be enriched with osteoblast-like cells formed colonies in soft agarose.(ABSTRACT TRUNCATED AT 400 WORDS)