Coxsackievirus and adenovirus receptor (CAR)-positive immature osteoblasts as targets of adenovirus-mediated gene transfer for fracture healing

T. Ito, K. Tokunaga, H. Maruyama, H. Kawashima, H. Kitahara, T. Horikoshi, A. Ogose, Y. Hotta, R. Kuwano, H. Katagiri, N. Endo

研究成果: Article査読

22 被引用数 (Scopus)

抄録

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 (104-108 PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. β-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.

本文言語English
ページ(範囲)1623-1628
ページ数6
ジャーナルGene Therapy
10
18
DOI
出版ステータスPublished - 2003 9
外部発表はい

ASJC Scopus subject areas

  • 分子医療
  • 分子生物学
  • 遺伝学

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