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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2003-8-8
pubmed:abstractText
Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5, 10, 14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteopontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1623-8
pubmed:dateRevised
2011-7-1
pubmed:meshHeading
pubmed-meshheading:12907955-Adenoviridae, pubmed-meshheading:12907955-Animals, pubmed-meshheading:12907955-Base Sequence, pubmed-meshheading:12907955-Bone and Bones, pubmed-meshheading:12907955-Fracture Healing, pubmed-meshheading:12907955-Gene Expression, pubmed-meshheading:12907955-Gene Therapy, pubmed-meshheading:12907955-Genetic Vectors, pubmed-meshheading:12907955-Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), pubmed-meshheading:12907955-Immunohistochemistry, pubmed-meshheading:12907955-In Situ Hybridization, pubmed-meshheading:12907955-Lac Operon, pubmed-meshheading:12907955-Mice, pubmed-meshheading:12907955-Models, Animal, pubmed-meshheading:12907955-Molecular Sequence Data, pubmed-meshheading:12907955-Osteoblasts, pubmed-meshheading:12907955-RNA, Messenger, pubmed-meshheading:12907955-Receptors, Virus, pubmed-meshheading:12907955-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12907955-Transduction, Genetic
pubmed:year
2003
pubmed:articleTitle
Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.
pubmed:affiliation
Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
pubmed:publicationType
Journal Article