title: Dual effect of adenovirus-mediated transfer of BMP7 in mixed neuron-glial cultures: neuroprotection and cellular differentiation.
abstract: 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.
authors.affiliation: Neural Regeneration Laboratory, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.forename: Dann-Ying
authors.initials: DY
authors.lastname: Liou
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Chuan-Wen
authors.initials: CW
authors.lastname: Chiu
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Yang
authors.forename: Hsu-An
authors.initials: HA
authors.lastname: Pan
authors.forename: Roanna I-Hsin
authors.initials: RI
authors.lastname: Liao
authors.forename: Huai-Sheng
authors.initials: HS
authors.lastname: Kuo
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Huang
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Hoffer
authors.forename: Henrich
authors.initials: H
authors.lastname: Cheng
mesh_terms: 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*
chemical_list: 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