OSTEOGENIN (BONE MORPHOGENIC PROTEIN-3) INHIBITS PROLIFERATION AND STIMULATES DIFFERENTIATION OF OSTEOPROGENITORS IN HUMAN BONE-MARROW

Treatment of human bone marrow osteoprogenitors with osteogenin (BMP-3 ; at 1, 2.5 and 10 ng/mI) caused dose-and time-dependent inhibition of DNA synthesis and cell proliferation, Simultaneously, osteogenin stim ulated type I collagen synthesis and cAMP production. Addition of oste ogenin to the cell culture increased intracellular alkaline phosphatas e activity and osteocalcin synthesis, with maximal stimulation at 2.5 ng/ml. Simultaneous addition of 2.5 ng/ml osteogenin and 1,25 dihydrox y vitamin D-3 (10(-8) M) enhanced the stimulation observed in osteocal cin synthesis. The experiments reported here demonstrate the significa nt ''in vitro'' influence of osteogenin in the stimulation of osteogen ic phenotype in osteoprogenitor cells which have been isolated from hu man bone marrow and cloned. These results support a reciprocal relatio nship between cell growth inhibition and expression of osteoblast diff erentiation.