Promotion of the osteogenetic activity of recombinant human bone morphogenetic protein by prostaglandin E1.

Abstract

We investigated the promotive effect of prostaglandin (PG) E1 on the osteogenetic activity of bone morphogenetic protein (BMP) using porous chemically synthesized hydroxyapatite ceramic (HAP) pellets as the carrier. After treating the pellets with recombinant human (rh) BMP-2 with or without PGE1, both of which were used at two different concentrations, they were inserted beneath the cranial periosteum of a rabbit. The degree of osteogenesis and osteoconductivity was then examined histopathologically as well as by means of an image-analyzing procedure. Results showed that there was extensive bone formation around the pellets as early as 3 weeks after insertion in the group, which received pellets treated with a relatively large amount of rhBMP alone as well as in the group receiving pellets treated with a small amount of rhBMP combined with PGE1. In the later group, the extent of bone formation was dose-dependent. Subsequent osteogenesis within the pores of the pellets in these groups slowly progressed over time, and by 9 weeks after the insertion, most of the pellet pores had filled with newly generated bone. In addition, the groups which received pellets treated with PGE1 alone also showed osteogenesis as demonstrated by osteoconduction, which was not observed in the group that received the phosphate buffered saline (PBS) treated pellets. The group that received pellets treated with a small amount of rhBMP plus a high concentration of PGE1 exhibited significantly greater bone induction than the group which received the pellets treated with a small amount rhBMP alone, and there was no statistically significant difference between the former group and the group that received a high rhBMP dose. These results clearly indicated that PGE1 has a strong and dose-dependent promotive effect on the osteogenetic activity of rhBMP and that it also promotes osteoconduction, even when used alone. This suggests that enormous reductions can be made in the amount of rhBMP administered when PGE1 is used in conjunction with porous HAP. This should prove to be very advantageous and practical in the clinical application of these materials.