title: Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation.
abstract: A 25-kDa homodimeric protein was purified from demineralized bovine bone extract and identified as activin A. The bovine bone activin enhanced formation of ectopic bone in rat subcutis when implanted in combination with partially purified bovine bone morphogenetic protein (BMP-2, BMP-3) in collagen/ceramic carrier. The implants, removed at 14 days, contained markedly elevated levels of alkaline phosphatase activity. Histological examination revealed an extensive formation of woven bone with very little cartilage. In contrast, a combination of transforming growth factor-beta 2 and BMP promoted formation of bone with an abundance of cartilage. The implants with BMP alone exhibited some osteoinductive activity, while the implants with activin alone showed no activity. These results demonstrate that bone is a rich source of activin and that activin plays an important role in modulating bone formation.
authors.affiliation: Celtrix Pharmaceuticals, Palo Alto, California 94303.
authors.forename: Y
authors.initials: Y
authors.lastname: Ogawa
authors.forename: D K
authors.initials: DK
authors.lastname: Schmidt
authors.forename: R M
authors.initials: RM
authors.lastname: Nathan
authors.forename: R M
authors.initials: RM
authors.lastname: Armstrong
authors.forename: K L
authors.initials: KL
authors.lastname: Miller
authors.forename: S J
authors.initials: SJ
authors.lastname: Sawamura
authors.forename: J M
authors.initials: JM
authors.lastname: Ziman
authors.forename: K L
authors.initials: KL
authors.lastname: Erickson
authors.forename: E R
authors.initials: ER
authors.lastname: de Leon
authors.forename: D M
authors.initials: DM
authors.lastname: Rosen
mesh_terms: D028341:Activins; D000595:Amino Acid Sequence; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins; D001842:Bone and Bones / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D002850:Chromatography, Gel; D003488:Cyanogen Bromide; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D066298:In Vitro Techniques; D007265:Inhibins / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016212:Transforming Growth Factor beta / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D019485:Bone Morphogenetic Proteins; D006133:Growth Substances; D010446:Peptide Fragments; D011506:Proteins; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D003488:Cyanogen Bromide