Human recombinant transforming growth factor α stimulates bone resorption and inhibits formation in vitro

Human recombinant transforming growth factor α (TGFα), which binds to the epidermal growth factor (EGF) receptor and causes several biological effects similar to those caused by EGF, was compared with murine EGF for its effects on a number of parameters of bone cell metabolism. TGFα stimulated bone resorption in two organ culture systems, the fetal rat long bone and neonatal mouse calvarial systems. TGFα stimulated bone resorption at concentrations as low as 0.1 ng/ml. TGFα effects on bone resorption in mouse calvariae were inhibited by indomethacin, suggesting that, like EGF, its effects were mediated by prostaglandin synthesis. TGFα had a different time course of action on bone resorption from that of EGF, causing more rapid release of previously incorporated ⁴⁵Ca from bone cultures, suggesting that TGFα does not function on bone as a simple EGF analogue. TGFα also caused effects on osteoblast function resembling those of EGF. It inhibited alkaline phosphatase activity in cultured rat osteosarcoma cells with the osteoblast phenotype and inhibited collagen synthesis in fetal rat calvaria at concentrations of 1.0 ng/ml. The lowest concentration of TGFα (expressed as nanogram equivalents of EGF per ml) required to produce a response in all of the systems tested was about 1/10th of that needed for EGF to produce a similar effect. These results indicate that TGFα is a potent stimulator of bone resorption and inhibitor of bone formation as assessed by inhibition of collagen synthesis and alkaline phosphatase activity and are consistent with the hypothesis that TGFα may be responsible, at least in part, for the bone resorption associated with some tumors.