| RRC ID |
41933
|
| 著者 |
Ito T, Tokunaga K, Maruyama H, Kawashima H, Kitahara H, Horikoshi T, Ogose A, Hotta Y, Kuwano R, Katagiri H, Endo N.
|
| タイトル |
Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing.
|
| ジャーナル |
Gene Ther
|
| Abstract |
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.
|
| 巻・号 |
10(18)
|
| ページ |
1623-8
|
| 公開日 |
2003-9-1
|
| DOI |
10.1038/sj.gt.3302060
|
| PII |
3302060
|
| PMID |
12907955
|
| MeSH |
Adenoviridae / genetics
Animals
Base Sequence
Bone and Bones / metabolism
Bone and Bones / pathology
Coxsackie and Adenovirus Receptor-Like Membrane Protein
Fracture Healing*
Gene Expression
Genetic Therapy / methods*
Genetic Vectors / administration & dosage
Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / analysis
Immunohistochemistry / methods
In Situ Hybridization / methods
Lac Operon
Mice
Models, Animal
Molecular Sequence Data
Osteoblasts / metabolism*
RNA, Messenger / analysis
Receptors, Virus / analysis
Receptors, Virus / genetics
Receptors, Virus / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Transduction, Genetic / methods*
|
| IF |
4.128
|
| 引用数 |
19
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126) |
