Human Platelet-Derived Transforming Growth Factor-βStimulates Parameters of Bone Growth in Fetal Rat Calvariae*

Abstract

Human platelet-derived transforming growth factor type .beta. (TGF.beta.) is mitogenic for fetal rat calvariae in serum-free organ culture. It enhances DNA synthesis in short (24-h) and long (48- to 96-h) term cultures, but produces no significant stimulatory effects on bone collagen synthesis or alkaline phosphatase activity (two parameters of differentiated osteoblastic cell-type function) when present continuously in culture. Transitory treatment with TGF.beta., however, induces a subsequent stimulation of collagen and noncollagen protein synthesis that depends on prior cell replication, suggesting an increase in the number of newly differentiated bone cells. In addition, TGF.beta. increases prostaglandin release, but this effect is probably unrelated to its mitogenic function. TGF.beta. activity is also found in culture medium conditioned by fetal rat calvariae, and the bone-derived factor produces effects similar to those of the human platelet factor. This polypeptide, therefore, may have an important function in early stages of bone development as well as bone repair after trauma-induced platelet degranulation.