Document Detail


Bone morphogenetic proteins mediate cellular response and, together with Noggin, regulate astrocyte differentiation after spinal cord injury.
MedLine Citation:
PMID:  20005873     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bone morphogenetic proteins (BMPs) play a critical role in regulating cell fate determination during central nervous system (CNS) development. In light of recent findings that BMP-2/4/7 expressions are upregulated after spinal cord injury, we hypothesized that the BMP signaling pathway is important in regulating cellular composition in the injured spinal cord. We found that BMP expressions were upregulated in neural stem cells (NSCs), neurons, oligodendrocytes and microglia/macrophages. Increased expression levels of pSmad1/5/8 (downstream molecules of BMP) were detected in neurons, NSCs, astrocytes, oligodendrocytes and oligodendroglial progenitor cells (OPCs). Active astrocytes which form the astroglial scar were probably derived from NSCs, OPCs and resident astrocytes. Since quiescent NSCs in the normal adult spinal cord will proliferate and differentiate actively into neural cells after traumatic injury, we proposed that BMPs can regulate cellular components by controlling NSC differentiation. Neurosphere culture from adult mouse spinal cord showed that BMP-4 promoted astrocyte differentiation from NSCs while suppressing production of neurons and oligodendrocytes. Conversely, inhibition of BMP-4 by Noggin notably decreased the ratio of astrocyte to neuron numbers. However, intrathecal administration of Noggin in the injured spinal cord failed to attenuate glial fibrillar acidic protein (GFAP) expression even though it effectively reduced pSmad expression. Noggin treatment did not block phosphorylation of Stat3 and the induction of GFAP in the injured spinal cord, suggesting that in addition to the BMP/Smad pathway, the JAK/STAT pathway may also be involved in the regulation of GFAP expression after spinal cord injury.
Authors:
Qi Xiao; Yang Du; Wutian Wu; Henry K Yip
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Publication Detail:
Type:  Journal Article     Date:  2009-12-11
Journal Detail:
Title:  Experimental neurology     Volume:  221     ISSN:  1090-2430     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-27     Completed Date:  2010-02-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  353-66     Citation Subset:  IM    
Copyright Information:
Copyright 2009 Elsevier Inc. All rights reserved.
Affiliation:
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / drug effects*
Bone Morphogenetic Proteins / pharmacology*,  therapeutic use*
Bromodeoxyuridine / metabolism
Carrier Proteins / pharmacology*,  therapeutic use*
Cell Differentiation / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Disease Models, Animal
Female
Gene Expression Regulation / drug effects
Mice
Mice, Inbred C57BL
Myelin Basic Proteins / genetics,  metabolism
Nerve Tissue Proteins / genetics,  metabolism
Neurons
Nuclear Proteins / genetics,  metabolism
Oligodendroglia / drug effects
RNA, Messenger / metabolism
Signal Transduction / drug effects,  physiology
Spinal Cord Injuries* / drug therapy,  pathology,  physiopathology
Stem Cells / drug effects
Time Factors
Chemical
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/Carrier Proteins; 0/Myelin Basic Proteins; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/RNA, Messenger; 148294-77-3/noggin protein; 59-14-3/Bromodeoxyuridine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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