title: B2A, a receptor modulator, increases the growth of pluripotent and preosteoblast cells through bone morphogenetic protein receptors.
abstract: B2A (B2A2-K-NS) is a synthetic, multidomain peptide which is being developed to augment spinal fusion and bone repair locally. Using pluripotent mesenchymal cells of murine and human origin, we show that B2A-induced cell proliferation in a modest but dose-dependent manner. However, essentially all human tumor lines tested were not responsive or were weakly responsive to B2A. B2A treatment activated extracellular signal-regulated kinases 1 and 2 (ERK1/2), and the proliferation was partially blocked by an mitogen-activated protein kinase (MEK) inhibitor. The bone morphogenetic protein (BMP) type I receptor kinase inhibitors depressed B2A-induced proliferation. Upregulation of bone morphogenetic protein 2 was not involved, as noggin, DAN, or chordin did not block B2A-induced proliferation. These data suggest that B2A-induced proliferation results from cell-type-specific activation of bone morphogenetic protein receptor, which, in turn, regulates ERK1/2 activity. B2A-induced proliferation, acting through ERK1/2, is a phenomenon that, while not strictly related to the ability of B2A to augment BMP-induced differentiation via the small mothers against decapentaplegic pathway, may ultimately contribute to bone repair in vivo.
authors.affiliation: BioSurface Engineering Technologies, Inc., 9430 Key West Avenue, Suite 220, Rockville, MD 20850, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: P O
authors.initials: PO
authors.lastname: Zamora
mesh_terms: D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D039904:Pluripotent Stem Cells / Q000166:cytology; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: C519235:B2A2-K-NS; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011994:Recombinant Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D052004:Bone Morphogenetic Protein Receptors