Cell differentiation in response to partially purified osteosarcoma-derived bone morphogenetic protein in vivo and in vitro.
Bone morphogenetic protein (BMP) and associated noncollagenous proteins (NCP) were isolated from human osteosarcoma tissue. Implantation of 5- and 10-mg samples induced heterotopic ossification in the mouse quadriceps. Osteosarcoma-derived BMP/NCP induced the same process of osteogenesis as human BMP/NCP isolated from bone matrix in vivo. In vitro continuous perfusion of neonatal rat muscle tissue with 5 micrograms/ml osteosarcoma-derived BMP/NCP increased glycosaminoglycan (GAG) synthesis significantly whereas DNA synthesis was relatively unchanged. Similar results were found when muscle tissue was preincubated with 200 micrograms of osteosarcoma-derived BMP/NCP for four hours followed by an incubation period of 14 days in BMP-free medium: GAG synthesis increased significantly, whereas DNA synthesis did not change. The increase in GAG synthesis coincided with cell differentiation but not cell proliferation. Histologic findings confirmed chondrogenesis in vitro. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that osteosarcoma-derived BMP/NCP included a prominent component with a molecular weight of 18,000 d.
Department of Oral and Maxillofacial Surgery, Bayerische Julius-Maximilians University, Würzburg, Federal Republic of Germany.
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D000818:Animals; D000831:Animals, Newborn; D019485:Bone Morphogenetic Proteins; D002356:Cartilage / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009024:Morphogenesis; D009363:Neoplasm Proteins / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D012516:Osteosarcoma / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019485:Bone Morphogenetic Proteins; D006025:Glycosaminoglycans; D009363:Neoplasm Proteins; D011506:Proteins; D004247:DNA