Effects of Transforming Growth Factor β on Human Bone Cells and Cells Derived from a Hyperplastic Callus of an Osteogenesis Type IV Patient

Abstract

As shwon in recent publications, transforming growth factor beta (TGF β) plays an important role in the regulation of growth and differentiation of fetal rodent calvaria cells. In this communication we describe the effects of TGF β on human osteoblasts (hOb) and callus cells. The incubation with TGF β for 72h a) stimulated proliferation of hOb, reaching maximal effects at the concentration of 0,5 ng/ml, b) induced a decrease of activity of the bone marker enzyme alkaline phosphatase, which plays a crucial role in the formation of mineralized matrix and c) simultaneously suppressed the synthesis of collagen, the main constituent of the organic matrix. These effects indicate that TGF β down-regulated the capacity of cultured human osteoblasts to produce a bone-like matrix and stimulated these cells to divide. The hereditary skeletal dysplasia of osteogenesis imperfecta (OI) is characterized by pathological low production of extracellular bone matrix and elevated number of osteoblasts. A rare but typical complication in OI is the formation of a hyperplastic callus, which involves desmal and endochondral ossification. The response of OI-derived osteoblasts and cells from the well mineralized part of a hyperplastic callus to TGF β was similar to that of normal human osteoblasts. In contrast to all other cells, TGF β stimulated alkaline phosphatase activity, collagen and protein synthesis in cells from the peripheral, immature part of the hyperplastic callus. These results indicate, that effects of TGF β on cultured human bone and callus cells strongly depend on their state of differentiation.