PMID- 22040684
OWN - NLM
STAT- MEDLINE
DCOM- 20120501
LR  - 20120109
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 8
IP  - 2
DP  - 2012 Feb
TI  - Surface immobilization of bone morphogenetic protein 2 via a self-assembled 
      monolayer formation induces cell differentiation.
PG  - 772-80
LID - 10.1016/j.actbio.2011.10.019 [doi]
AB  - Bone extracellular matrix consists of a network of proteins in which growth 
      factors, like bone morphogenetic protein 2 (BMP-2), are embedded and released 
      upon matrix turnover and degradation. Recombinant human (rh)BMP-2 shows promise 
      in enhancing bone fracture repair, although issues regarding finding a suitable 
      delivery system still limit its extensive clinical use. The aim of this study is 
      to determine which cell activities are triggered by the presentation of 
      immobilized rhBMP-2. For this purpose gold surfaces were first decorated with a 
      self-assembled monolayer consisting of a hetero-bifunctional linker. rhBMP-2 was 
      covalently bound to the surfaces via this linker and used to investigate the 
      cellular responses of C2C12 myoblasts. We show that covalently immobilized 
      rhBMP-2 (iBMP-2) initiates short-term signaling events. Using a BMP-responsive 
      reporter gene assay and western blotting to monitor phosphorylation of Smad1/5/8 
      we prove that iBMP-2 activates BMP-dependent signal transduction. Furthermore, we 
      demonstrate that iBMP-2 suppresses myotube formation and promotes the osteoblast 
      phenotype in C2C12 cells. The bioactivity of surface-bound rhBMP-2 presented in 
      this study is not due to its release into the medium. As such, our simple 
      approach paves the way for the controlled local presentation of immobilized 
      growth factors, limiting degradation while still maintaining biological activity.
CI  - Copyright (c) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights 
      reserved.
FAU - Pohl, Theresa L M
AU  - Pohl TL
AD  - Department of Biophysical Chemistry, Institute for Physical Chemistry, University 
      of Heidelberg, INF 253, 69120 Heidelberg, Germany.
FAU - Boergermann, Jan H
AU  - Boergermann JH
FAU - Schwaerzer, Gerburg K
AU  - Schwaerzer GK
FAU - Knaus, Petra
AU  - Knaus P
FAU - Cavalcanti-Adam, Elisabetta A
AU  - Cavalcanti-Adam EA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111020
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Culture Media)
RN  - 0 (Immobilized Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Smad Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (recombinant human bone morphogenetic protein-2)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 2/*pharmacology
MH  - Cell Differentiation/*drug effects
MH  - Culture Media/chemistry
MH  - Humans
MH  - Immobilized Proteins/*pharmacology
MH  - Luciferases/metabolism
MH  - Mice
MH  - Muscle Fibers, Skeletal/drug effects/metabolism
MH  - Osteogenesis/drug effects
MH  - Recombinant Proteins/pharmacology
MH  - Response Elements/genetics
MH  - Signal Transduction/drug effects
MH  - Smad Proteins/metabolism
MH  - Surface Properties/drug effects
MH  - Transcription, Genetic/drug effects
MH  - Transforming Growth Factor beta/*pharmacology
EDAT- 2011/11/02 06:00
MHDA- 2012/05/02 06:00
CRDT- 2011/11/02 06:00
PHST- 2011/07/19 00:00 [received]
PHST- 2011/10/12 00:00 [revised]
PHST- 2011/10/13 00:00 [accepted]
PHST- 2011/11/02 06:00 [entrez]
PHST- 2011/11/02 06:00 [pubmed]
PHST- 2012/05/02 06:00 [medline]
AID - S1742-7061(11)00450-8 [pii]
AID - 10.1016/j.actbio.2011.10.019 [doi]
PST - ppublish
SO  - Acta Biomater. 2012 Feb;8(2):772-80. doi: 10.1016/j.actbio.2011.10.019. Epub 2011 
      Oct 20.