TGF-β and PDGF act synergistically in affecting the growth of human osteoblast-enriched cultures

Transforming growth factor beta (TGF-β is a polypeptide found in high concentrations in bone and is produced by and acts on primary adult human derived osteoblast-enriched cultures (PHO cells). Receptors for TGF-β are present on PHO cells and TGF-β is mitogenic for these cells. Results of these studies in conjunction with those of others suggest that TGF-β may have an important therapeutic role in orthopaedic surgery; however, with respect to its mitogenic actions, further studies were needed to establish whether TGF-β was acting directly to stimulate the growth of PHO cells. TGF-β has been found in other systems to act as an indirect mitogen, stimulating growth via secretion of another growth factor, platelet-derived growth factor (PDGF). In an effort to determine whether the TGF-β growth stimulation was mediated directly or indirectly, we have examined the growth stimulation of PHO cells by PDGF alone and in combination with TGF-β These studies revealed that TGF-p in combination with either PDGF-AA or BB led to stimulation greater than that observed with either growth factor alone. TGF-P in combination with PDGF-BB led to a synergistic stimulatory response while that observed with the AA isoform was more nearly additive. Further studies demonstrated that TGF-β was capable of up-regulating the protein levels of the PDGF alpha (α receptor within thirty minutes of TGF-β pretreatment. Thus, TGF-β appears to have both direct and indirect mechanisms of action as a mitogen in the PHO system. Finally, we showed that both the positive and negative alkaline phosphatase staining PHO cells were responsive to the mitogenic effects of both growth factor singly and in combination.