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.

Keywords::

• B2A
• peptide
• cell proliferation
• osteoblasts
• bioengineering

Acknowledgements

Parts of this work were conducted under contract with the University of Maryland, Baltimore, MD; and SA Biosciences Corporation, Frederick, MD.

Declaration of interest All the authors report the following conflicts: all authors are or have been employees of BioSET, Inc. and either own stock/stock options or have other equity in BioSET, Inc. All funding sources supporting publication of a work or study: BioSurface Engineering Technologies, Inc., Rockville, MD, USA.