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Effects of transforming growth factor beta on cells derived from bone and callus of patients with osteogenesis imperfecta

We studied the influence of transforming growth factor beta (TGF‐β) on cultured bone cells derived from two patients with osteogenesis imperfecta (OI) and from human controls. Additionally, cells from a hyperplastic callus that had developed spontaneously at the femur of the patient in Case 1 and cells from a normal fracture callus were included in the study. TGF‐β increased the synthesis of total protein and collagen of all cells without changing the pattern of interstitial collagens. Proliferation was stimulated by TGF‐β in the OI bone cells from Case 1, in cells from the central part of the hyperplastic callus, and in cells from the fracture callus. In Case 2, proliferation of bone cells was decreased by low concentrations of TGF‐β. Alkaline phosphatase (AP) activity was enhanced by TGF‐β in normal human bone cells, not affected in bone cells from the patient in Case 2 or in cells from the central part of the hyperplastic callus, and inhibited in bone cells and cells from the peripheral part of the hyperplastic callus of Case 1 and in cells from the fracture callus. We conclude that TGF‐β 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‐β was restricted to normal human bone cells and might reflect their mature state of osteoblastic differentiation. Cells derived from bone of both patients with OI, from the hyperplastic callus, and from the fracture callus showed a different response pattern to TGF‐β. The difference in response to TGF‐β 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). This study indicates that the effects of TGF‐β 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 hyperplastic callus in OI.