Bone Morphogenetic Protein-7 Modifies the Effects of Insulin-Like Growth Factors and Intermittent Parathyroid Hormone (1-34) on Human Periodontal Ligament Cell Physiology In Vitro

Background: Components of the insulin-like growth factor (IGF) system and intermittent parathyroid hormone (PTH) were demonstrated to exert anabolic effects on the periodontal ligament (PDL) and, thereby, contribute to the regeneration of structures that were lost because of inflammatory periodontal disease. Methods: In the present study, a PDL cell culture is created to examine whether a combination of IGFs and intermittent PTH would enhance the cellular response elicited by each factor alone and addressed the question of whether a pretreatment of the cells with bone morphogenetic protein (BMP)-7 alters the PDL cell phenotype and behavior on IGF-PTH stimulation. Results: IGF-I and IGF-II enhanced proliferation and differentiation in preconfluent and confluent cultures. A BMP-7 pretreatment inhibited those effects in preconfluent cells but not in confluent cultures. Intermittent PTH (1-34) inhibited the proliferation but stimulated the differentiation of preconfluent cells, whereas the opposite effect was observed in confluent cultures. BMP-7 prestimulation made preconfluent cells respond like confluent cultures on intermittent PTH (1-34) challenge. A combined administration of PTH (1-34) and IGF-I or IGF-II mostly mirrored the effects seen for one of the individual agents alone, but synergistic effects were not observed. Conclusions: The present data indicate that both PTH (134) and IGF-I or IGF-II exert a maturation stage-dependent effect on PDL cell proliferation and differentiation. Combining PTH (1-34) and IGF does not seem to potentiate the effects seen for the agents alone. Furthermore, our data suggest that BMP-7 induces preconfluent cells to acquire a more differentiated phenotype and to respond to intermittent PTH (1-34) accordingly. Confluent cultures seem to be less susceptible to BMP-7. J Periodontol 2011;82:900-908.