Would three BMPs at low concentration be better than one at high concentration? An experimental study with rat osteoprogenitor cells.

Abstract

Background: Bone morphogenetic proteins (BMPs) are used in clinical practice for the stimulation of bone formation, but can often lead to serious complications. Recent studies have demonstrated that BMPs involved in the early stages of bone formation are species-specific. In cattle the most common forms encountered are BMP7, growth differentiation factor 5 (GDF5), and NEL-like protein 1 (NELL1), while in rats the most common are BMP2, BMP5 and BMP6. The aim of this study was to compare the action of species-specific BMPs on osteoprogenitor cells. Thus, rat osteoprogenitor cells were exposed to one BMP in a high dose, and three of them at one third of the high dose.

Materials and methods: Isolated rat osteoprogenitor cells were treated in culture with different concentrations of BMP2, BMP5 and BMP6 or with lower concentrations of combinations of these cytokines. The activity of alkaline phosphatase, calcium deposition and mRNA level for transcription factor SP7 (osterix) and tissue non-specific alkaline phosphatase (TNAP) served as indicators of BMPs effect.

Results: BMPs stimulated all studied parameters compared to control cultures, but no statistically significant differences were observed between the action of a large dose of one cytokine and a combination of cytokines given at lower concentrations.

Conclusions: Three BMPs used in a low dose exert a similar effect to one used in a high dose. Since the BMPs stimulate different receptors, and activate different signalling pathways, using a mixture of properly chosen BMPs at a low concentration may give better results than a single one at a high concentration, and may avoid untoward effects.