title: Synergistic enhancement of human bone marrow stromal cell proliferation and osteogenic differentiation on BMP-2-derived and RGD peptide concentration gradients.
abstract: Rational design of bioactive tissue engineered scaffolds for directing bone regeneration in vivo requires a comprehensive understanding of cell interactions with the immobilized bioactive molecules. In the current study, substrates possessing gradient concentrations of immobilized peptides were used to measure the concentration-dependent proliferation and osteogenic differentiation of human bone marrow stromal cells. Two bioactive peptides, one derived from extracellular matrix protein (ECM), GRGDS, and one from bone morphogenic protein-2 (BMP-2), KIPKASSVPTELSAISTLYL, were found to synergistically enhance cell proliferation, up-regulate osteogenic mRNA markers bone sialoprotein (BSP) and Runt-related transcription factor 2, and produce mineralization at densities greater than 130 pmol cm(-2) (65 pmol cm(-2) for each peptide). In addition, COOH-terminated self-assembled monolayers alone led to up-regulated BSP mRNA levels at densities above 200 pmol cm(-2) and increased cell proliferation from day 3 to day 14. Taking further advantage of both the synergistic potentials and the concentration-dependent activities of ECM and growth-factor-derived peptides on proliferative activity and osteogenic differentiation, without the need for additional osteogenic supplements, will enable the successful incorporation of the bioactive species into biorelevant tissue engineering scaffolds.
authors.affiliation: Polymers Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8543, USA. nicole.moore@nih.gov
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Moore
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Lin
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Gallant
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Becker
mesh_terms: D000595:Amino Acid Sequence; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D007150:Immunohistochemistry; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D056951:Photoelectron Spectroscopy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D058574:Integrin-Binding Sialoprotein; D009842:Oligopeptides; D012333:RNA, Messenger; C493709:RUNX2 protein, human; C047981:arginyl-glycyl-aspartic acid