Osteoinduction by Bone Morphogenetic Protein-2 via Adenoviral Vector under Transient Immunosuppression

doi:10.1006/bbrc.1999.1975

Biochemical and Biophysical Research Communications

Volume 267, Issue 1, 7 January 2000, Pages 382-387

https://doi.org/10.1006/bbrc.1999.1975 Get rights and content

Abstract

To examine the effectiveness of gene transfer of bone morphogenetic protein (BMP)-2 in vivo, we evaluated osteoinduction by an adenoviral vector, AxCAOBMP-2, under transient immunosuppression with an immunosuppression drug (cyclophosphamide), which was given at a dose of 125 mg/kg intraperitoneally the day before vector injection. Twenty-five microliters of AxCAOBMP-2 (8.75 × 10⁸ pfu, Group I) and AxCALacZ (1.75 × 10⁸ pfu, control group) and 5 μl of AxCAOBMP-2 (1.75 × 10⁸ pfu, Group II) were injected into a right calf muscle. On day 21, induced bone in each group was investigated radiologically, histologically, and biochemically. The finding of osteoinduction was only seen in the AxCAOBMP-2-treated groups with immunosuppression. The activity of osteoinduction in Group I was higher than that in Group II. These results suggest that gene therapy with AxCAOBMP-2 under transient immunosuppression may be useful for bone reconstruction.

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^☆: Abbreviations used: BMP, bone morphogenetic protein; ALP, alkaline phosphatase; MOI, multiplicity of infection; AxCAOBMP-2, a replication-deficient adenoviral vector-carrying BMP-2 gene; AxCALacZ, a replication-deficient adenoviral vector-carrying the Escherichia coli; E. coli, Escherichia coli; X-gal, 5-bromo-4chloro-3-indolyl-β-d-(−)-galactopyranoside; pfu, plaque-forming units

¹: To whom correspondence should be addressed. Fax: +81-75-761-9732. E-mail: [email protected].

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Regular ArticleOsteoinduction by Bone Morphogenetic Protein-2 via Adenoviral Vector under Transient Immunosuppression☆

Abstract

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endo.

Cell

Bone

Biochem. Biophys. Res. Commun.

Immunity

Science

Science

Proc. Natl. Acad. Sci. USA

Somat. Cell Mol. Gen.

New Engl. J. Med.

J. Orthop. Res.

Gene Ther.

Proc. Natl. Acad. Sci. USA

J. Clin. Invest.

Calicif. Tissue Int.

Regular Article
Osteoinduction by Bone Morphogenetic Protein-2 via Adenoviral Vector under Transient Immunosuppression☆