Recombinant Human Bone Morphogenetic Protein Induces Bone Formation

• Published in: Proceedings of the National Academy of Sciences - PNAS 1990-03, Vol.87 (6), p.2220-2224
• Main Authors: Wang, Elizabeth A., Rosen, Vicki, D'Alessandro, Josephine S., Bauduy, Marc, Cordes, Paul, Harada, Tomoko, Israel, David I., Hewick, Rodney M., Kerns, Kelvin M., LaPan, Peter, Luxenberg, Deborah H., McQuid, David, Moutsatsos, Ioannis K., Nove, John, Wozney, John M.
• Format: Article
• Language: English
• Subjects: 550201 - Biochemistry- Tracer Techniques; AMINO ACIDS; ANIMAL CELLS; ANIMAL TISSUES; ANIMALS; Antibodies; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOSYNTHESIS; BODY; bone; Bone and Bones - cytology; Bone Development - drug effects; Bone formation; Bone Morphogenetic Proteins; BONE TISSUES; Bones; CARBOXYLIC ACIDS; CARTILAGE; Cartilage - cytology; Cartilage - drug effects; Cartilage - growth & development; Cell Line; Cell lines; CHO CELLS; Chondrocytes; CLONING; CONNECTIVE TISSUE; DAYS LIVING RADIOISOTOPES; DNA; DNA HYBRIDIZATION; DNA-CLONING; DOSE-RESPONSE RELATIONSHIPS; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; ELECTROPHORESIS; EVEN-ODD NUCLEI; Growth Substances - pharmacology; HISTOLOGY; Humans; HYBRIDIZATION; INTERMEDIATE MASS NUCLEI; IODINE 125; IODINE ISOTOPES; ISOTOPES; LIGHT NUCLEI; LIPOTROPIC FACTORS; MAMMALS; MAN; METHIONINE; MOLECULAR STRUCTURE; Molecular Weight; NUCLEI; NUCLEIC ACIDS; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PRIMATES; PROTEINS; Proteins - genetics; Proteins - isolation & purification; Proteins - pharmacology; RADIOISOTOPES; Rats; RECOMBINANT DNA; Recombinant Proteins - isolation & purification; Recombinant Proteins - pharmacology; SULFUR 35; SULFUR ISOTOPES; SYNTHESIS; TISSUES; Ungulates; VERTEBRATES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.6.2220

We have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 μg of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans.