Abstract:A purified bone‐inducing protein complex (BIC), isolated from bovine bone and causing de novo bone formation in vivo, induces defined effects on rat mesenchymal cells in vitro. Spindle‐like mesenchymal cells growing in monolayers change to polygonal cells, forming a multilayered growth pattern. The mesenchymal cells acquire alkaline phosphatase activity. Upon culture with BIC, the typical collagen Type III deposition of these mesenchymal cells is remarkably reduced whereas the collagen Type I expression remains unaffected. All these in vitro effects are consistent with the strong bone‐forming capacity of BIC in vivo. A combination of two cytokines, transforming growth factorβl (TGFβl) and epidermal growth factor (EGF), shows a similar activity to BIC. Neutralizing anti‐TGFβantibodies interfere with all in vitro effects of BIC. The neutralization of BIC and the inductive capacity of the combination of TGFβl plus EGF point to the substantial role of TGFβor TGFβ‐like molecules in BIC; whether the active polypeptides are identical to TGFP or somewhat structurally homologous to TGFβremains
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