Pleiotrophin Regulates Bone Morphogenetic Protein (BMP)-Induced Ectopic Osteogenesis

Abstract

We previously isolated pleiotrophin (PTN) from bovine bone as a protein and showed that it stimulated osteoblastic growth and differentiation. Further details of its function, however, have not been fully clarified. The aim of this paper was to elucidate the effects of PTN on bone morphogenetic protein (BMP)-induced ectopic osteogenesis. Recombinant human BMP (rhBMP)-2 (1.2μg) was combined with a fibrous glass membrane, which had been established as an effective carrier. Various amounts of the purified bovine PTN (5, 10, 50, and 100μg) or rhPTN (5 and 10μg) were added to the rhBMP-2/carrier composites and implanted into rats subcutaneously as reported. It was found that the amount of bone induced in the system increased with the addition of 10μg of either purified PTN or rhPTN. However, the amount of bone decreased with the addition of 50 or 100μg of purified PTN dose-dependently, as judged by both alkaline phosphatase activity and calcium content in the retrieved implants. It was concluded that purified PTN or rhPTN, at ratios of concentration of 10-100μg of PTN to 1.2μg of rhBMP-2 in the carrier, regulated the ectopic bone-inducing activity of rhBMP-2.