PMID- 18028109
OWN - NLM
STAT- MEDLINE
DCOM- 20080225
LR  - 20211020
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 26
IP  - 11
DP  - 2007 Dec
TI  - A potential role for bone morphogenetic protein signalling in glial cell fate 
      determination following adult central nervous system injury in vivo.
PG  - 3024-35
AB  - Bone morphogenetic proteins (BMPs) and their endogenous inhibitors, including 
      noggin, chordin and follistatin, have roles in pattern formation and fate 
      specification of neuronal and glial cells during nervous system development. We 
      have examined their influence on glial reactions in the injured central nervous 
      system (CNS). We show that penetrating injuries to the brain and spinal cord 
      resulted in the upregulation of BMP-2/4, BMP-7, and noggin, with the latter being 
      expressed almost exclusively by reactive astrocytes at the injury site, and we 
      show that astrocytes in vitro produce noggin. As BMPs have been shown to drive 
      cultured NG2-positive oligodendrocyte precursors (OPCs) towards a multipotential 
      phenotype (type II astrocytes), we investigated the effects of inhibiting noggin 
      with a function-blocking antibody (noggin-FbAb). In vitro, BMP-driven conversion 
      of OPCs to type 2 astrocytes was inhibited by noggin, an effect that was reversed 
      by noggin-FbAb. Noggin-FbAb also increased the number of type 2 astrocytes 
      generated from cultured OPCs exposed to an astrocyte feeder layer, consistent 
      with astrocytes producing both BMPs and noggin. In knife cut injuries in vivo, 
      noggin-FbAb treatment resulted in an increase in the number of NG2-positive cells 
      and small GFAP-positive cells in the injury site, and the appearance of glial 
      cells with the morphological and antigenic characteristics of type 2 astrocytes 
      (as generated in vitro), with coexpression of both GFAP and NG2. This potential 
      conversion of inhibitory OPCs to type 2 astrocyte-like cells in vivo suggests 
      that endogenous BMPs, unmasked by noggin antagonism, might be exploited to 
      manipulate cell fate following CNS trauma.
FAU - Hampton, David W
AU  - Hampton DW
AD  - ICORD, University of British Columbia, Vancouver, BC, Canada. dwh27@cam.ac.uk
FAU - Asher, Richard A
AU  - Asher RA
FAU - Kondo, Toru
AU  - Kondo T
FAU - Steeves, John D
AU  - Steeves JD
FAU - Ramer, Matt S
AU  - Ramer MS
FAU - Fawcett, James W
AU  - Fawcett JW
LA  - eng
GR  - G0300271/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Antibodies)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 148294-77-3 (noggin protein)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Adult Stem Cells/drug effects/physiology
MH  - Animals
MH  - Animals, Newborn
MH  - Antibodies/pharmacology
MH  - Bone Morphogenetic Proteins/pharmacology/*physiology
MH  - Bromodeoxyuridine/metabolism
MH  - Carrier Proteins/immunology/metabolism/physiology
MH  - Cell Differentiation/drug effects/physiology
MH  - Cells, Cultured
MH  - Drug Interactions
MH  - Gene Expression Regulation/drug effects/physiology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Mice
MH  - Neuroglia/drug effects/*physiology
MH  - Oligodendroglia/drug effects/physiology
MH  - Rats
MH  - Signal Transduction/drug effects/*physiology
MH  - Trauma, Nervous System/*metabolism/*pathology
EDAT- 2007/11/22 09:00
MHDA- 2008/02/26 09:00
CRDT- 2007/11/22 09:00
PHST- 2007/11/22 09:00 [pubmed]
PHST- 2008/02/26 09:00 [medline]
PHST- 2007/11/22 09:00 [entrez]
AID - EJN5940 [pii]
AID - 10.1111/j.1460-9568.2007.05940.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2007 Dec;26(11):3024-35. doi: 10.1111/j.1460-9568.2007.05940.x.