Dual effect of adenovirus-mediated transfer of BMP7 in mixed neuron-glial cultures: neuroprotection and cellular differentiation.
Bone morphogenetic proteins (BMPs), members of the TGF-beta superfamily, have been implicated in nervous system development and in response to injury. Previous studies have shown that recombinant BMP7 can enhance dendritic growth and protect cultured neurons from oxidative stress. Because of the presence of extracellular BMP antagonists, BMP7 seems to act locally. Therefore, the present study uses BMP7 overexpression using adenovirus (Ad)-mediated gene transfer to examine its effect in mixed neuronal cultures. Enhanced BMP7 expression selectively induces neuronal CGRP expression in a time-dependent manner. BMP7 overexpression not only significantly protects cultures from H2O2 toxicity but reduces lipopolysaccharide (LPS) stimulation. Concurrently, it profoundly reduces microglial numbers, but increases oligodendroglial and endothelial cells. Together, low-dose and continuously expressed BMP7 is both neuroprotective and differentiation-inductive.
Tsai
May-Jywan
MJ
Neural Regeneration Laboratory, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
Weng
Ching-Feng
CF
Shyue
Song-Kun
SK
Liou
Dann-Ying
DY
Chen
Chien-Hung
CH
Chiu
Chuan-Wen
CW
Yang
Tzu-Hsuan
TH
Pan
Hsu-An
HA
Liao
Roanna I-Hsin
RI
Kuo
Huai-Sheng
HS
Huang
Ming-Chao
MC
Huang
Wen-Cheng
WC
Hoffer
Barry J
BJ
Cheng
Henrich
H
D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques / Q000379:methods; D053331:Ectodysplasins / Q000378:metabolism; D004622:Embryo, Mammalian; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000502:physiology*
C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D053331:Ectodysplasins; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D016212:Transforming Growth Factor beta; D006861:Hydrogen Peroxide; D015740:Calcitonin Gene-Related Peptide