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

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)1623-1628
Number of pages6
JournalGene Therapy
Volume10
Issue number18
DOIs
Publication statusPublished - 2003 Sep

Keywords

  • Adenovirus vector
  • Coxsackievirus and adenovirus receptor (CAR)
  • Fracture healing
  • Immature osteoblast

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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