title: Cerebrospinal fluid contains biologically active bone morphogenetic protein-7.
abstract: Bone morphogenetic proteins (BMPs) regulate the development and function of many types of neurons. However, little is known of the actual concentrations of BMPs in the various parts of the brain. In this study, we considered the possibility that BMPs might be present in cerebrospinal fluid (CSF). Western blot analysis of normal adult bovine CSF revealed the presence of dimeric and monomeric forms of BMP-7, and the concentration of this molecule was found to be approximately 12 ng/ml in a radioimmunoassay. Since BMP-7 is known to induce dendritic growth in rat sympathetic neurons, this was used as a bioassay to examine the biological activity of the BMP-7 present in CSF. Addition of normal bovine CSF to cultures of sympathetic neurons produced a dose-dependent increase in dendritic growth and the magnitude of this response approximated that obtained with maximally effective concentrations of exogenous BMP-7. Moreover, CSF-induced dendritic growth was inhibited by follistatin, a protein that can sequester BMPs, and by either of two monoclonal antibodies that react with BMP-7. These results show that, unlike most other neurotrophic factors, BMP-7 is a constituent of normal CSF and is present at concentrations sufficient to elicit a near maximal biological response.
authors.affiliation: Creative Biomolecules Inc., Hopkinton, Massachusetts 01748, USA.
authors.forename: B
authors.initials: B
authors.lastname: Dattatreyamurty
authors.forename: E
authors.initials: E
authors.lastname: Roux
authors.forename: C
authors.initials: C
authors.lastname: Horbinski
authors.forename: P L
authors.initials: PL
authors.lastname: Kaplan
authors.forename: L A
authors.initials: LA
authors.lastname: Robak
authors.forename: H N
authors.initials: HN
authors.lastname: Beck
authors.forename: P
authors.initials: P
authors.lastname: Lein
authors.forename: D
authors.initials: D
authors.lastname: Higgins
authors.forename: V
authors.initials: V
authors.lastname: Chandrasekaran
mesh_terms: D028341:Activins / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000134:cerebrospinal fluid* / Q000494:pharmacology / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000502:physiology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D038681:Follistatin; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011863:Radioimmunoassay; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology; D016212:Transforming Growth Factor beta
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D016212:Transforming Growth Factor beta; D028341:Activins