EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA ON CELLS DERIVED FROM BONEAND CALLUS OF PATIENTS WITH OSTEOGENESIS IMPERFECTA

We studied the influence of transforming growth factor beta (TGF-beta) on cultured bone cells derived from two patients with osteogenesis im perfecta (OI) and from human controls. Additionally, cells from a hype rplastic callus that had developed spontaneously at the femur of the p atient in Case 1 and cells from a normal fracture callus were included in the study. TGF-beta increased the synthesis of total protein and c ollagen of all cells without changing the pattern of interstitial coll agens. Proliferation was stimulated by TGF-beta in the OI bone cells f rom Case 1, in cells from the central part of the hyperplastic callus, and in cells from the fracture callus. In Case 2, proliferation of bo ne cells was decreased by low concentrations of TGF-beta. Alkaline pho sphatase (AP) activity was enhanced by TGF-beta in normal human bone c ells, not affected in bone cells from the patient in Case 2 or in cell s from the central part of the hyperplastic callus, and inhibited in b one cells and cells from the peripheral part of the hyperplastic callu s of Case 1 and in cells from the fracture callus. We conclude that TG F-beta has common and specific effects on cultured human cells derived from different types of skeletal tissues. Simultaneous stimulation of collagen synthesis and AP activity by TGF-beta was restricted to norm al human bone cells and might reflect their mature state of osteoblast ic differentiation. Cells derived from bone of both patients with OI, from the hyperplastic callus, and from the fracture callus showed a di fferent response pattern to TGF-beta. The difference in response to TG F-beta of bone cells from the two patients with OI might be related to the development of a hyperplastic callus in one of them (Case 1). Thi s study indicates that the effects of TGF-beta on cells isolated from human skeletal tissues depend on their metabolic state and their stage of maturation and might be correlated with the formation of a hyperpl astic callus in OI.