CELL-DIFFERENTIATION IN RESPONSE TO PARTIALLY PURIFIED OSTEOSARCOMA-DERIVED BONE MORPHOGENETIC PROTEIN IN-VIVO AND IN-VITRO

Bone morphogenetic protein (BMP) and associated noncollagenous protein s (NCP) were isolated from human osteosarcoma tissue. Implantation of 5- and 10-mg samples induced heterotopic ossification in the mouse qua driceps. Osteosarcoma-derived BMP/NCP induced the same process of oste ogenesis as human BMP/NCP isolated from bone matrix in vivo. In vitro continuous perfusion of neonatal rat muscle tissue with 5 mug/ml osteo sarcoma-derived BMP/NCP increased glycosaminoglycan (GAG) synthesis si gnificantly whereas DNA synthesis was relatively unchanged. Similar re sults were found when muscle tissue was preincubated with 200 mug of o steosarcoma-derived BMP/NCP for four hours followed by an incubation p eriod of 14 days in BMP-free medium: GAG synthesis increased significa ntly, whereas DNA synthesis did not change. The increase in GAG synthe sis coincided with cell differentiation but not cell proliferation. Hi stologic findings confirmed chondrogenesis in vitro. Sodium dodecyl-su lfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that osteosarcoma-derived BMP/NCP included a prominent component with a mol ecular weight of 18,000 d.