BONE MORPHOGENETIC PROTEIN-2 BUT NOT BONE MORPHOGENETIC PROTEIN-4 ANDPROTEIN-6 STIMULATES CHEMOTACTIC MIGRATION OF HUMAN OSTEOBLASTS, HUMAN MARROW OSTEOBLASTS, AND U2-OS CELLS

Bone morphogenetic proteins (BMPs) have important functions for the di fferentiation of bone cells, but the exact role for bone remodeling an d bone healing still needs to be defined. Migration of bone forming ce lls is an important physiological event both during bone healing and b one remodeling. The chemotactic properties of the bone morphogenetic p rotein family of growth factors have not been investigated. In this st udy the chemotactic effects of the bone morphogenetic proteins BMP-2, -4, and -6 have been quantitated toward human osteoblasts, human marro w stromal osteoblasts, and U2-OS human osteosarcoma cells. BMP-2 stimu lated the migration of human stromal osteoblasts, human osteoblasts, a nd U2-OS cells with bell-shaped response curves in a dose-dependent ma nner with a 300% increase in cell migration at 1.0 ng/mL for human str omal osteoblasts and a 170-180% increase for human osteoblasts and U2- OS cells. At higher concentrations, migration decreased to background levels. BMP-4 and -6 did not show any effects on cellular migration. T his study shows that BMP-2 can stimulate in vitro migration of human o steoblasts and human osteosarcoma cells. BMP-2 might play a role in th e chemotactic recruitment of especially undifferentiated osteoblasts d uring bone remodeling and bone healing.