Osteoinduction by bone morphogenetic protein-2 via adenoviral vector under transient immunosuppression

被引:63
作者
Okubo, Y
Bessho, K
Fujimura, K
Iizuka, T
Miyatake, SI
机构
[1] Kyoto Univ, Grad Sch Med, Dept Oral & Maxillofacial Surg, Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Neurosurg & Clin Neurosci, Sakyo Ku, Kyoto 6068507, Japan
关键词
D O I
10.1006/bbrc.1999.1975
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 x 10(8) pfu, Group I) and AxCALacZ (1.75 x 10(8) pfu, control group) and 5 mu l of AxCAOBMP-2 (1.75 x 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. (C) 2000 Academic Press.
引用
收藏
页码:382 / 387
页数:6
相关论文
共 35 条
[1]   Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy [J].
Alden, TD ;
Pittman, DD ;
Beres, EJ ;
Hankins, GR ;
Kallmes, DF ;
Wisotsky, BM ;
Kerns, KM ;
Helm, GA .
JOURNAL OF NEUROSURGERY, 1999, 90 (01) :109-114
[2]   In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector [J].
Alden, TD ;
Pittman, DD ;
Hankins, GR ;
Beres, EJ ;
Engh, JA ;
Das, S ;
Hudson, SB ;
Kerns, KM ;
Kallmes, DF ;
Helm, GA .
HUMAN GENE THERAPY, 1999, 10 (13) :2245-2253
[3]  
CONNERTY HV, 1966, AM J CLIN PATHOL, V45, P290
[4]   TRANSFER OF GENES TO HUMANS - EARLY LESSONS AND OBSTACLES TO SUCCESS [J].
CRYSTAL, RG .
SCIENCE, 1995, 270 (5235) :404-410
[5]   GENE-THERAPY VIA PRIMARY MYOBLASTS - LONG-TERM EXPRESSION OF FACTOR-IX PROTEIN FOLLOWING TRANSPLANTATION INVIVO [J].
DAI, Y ;
ROMAN, M ;
NAVIAUX, RK ;
VERMA, IM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (22) :10892-10895
[6]   CELLULAR AND HUMORAL IMMUNE-RESPONSES TO ADENOVIRAL VECTORS CONTAINING FACTOR-IX GENE - TOLERIZATION OF FACTOR-IX AND VECTOR ANTIGENS ALLOWS FOR LONG-TERM EXPRESSION [J].
DAI, YF ;
SCHWARZ, EM ;
GU, DL ;
ZHANG, WW ;
SARVETNICK, N ;
VERMA, IM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (05) :1401-1405
[7]  
*EX BOARD AN SECT, 1988, JSCC, V1, P11
[8]   Stimulation of new bone formation by direct transfer of osteogenic plasmid genes [J].
Fang, JM ;
Zhu, YY ;
Smiley, E ;
Bonadio, J ;
Rouleau, JP ;
Goldstein, SA ;
McCauley, LK ;
Davidson, BL ;
Roessler, BJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :5753-5758
[9]   EXPERIMENTAL STUDIES ON BONE-INDUCING ACTIVITY OF COMPOSITES OF ATELOPEPTIDE TYPE-I COLLAGEN AS A CARRIER FOR ECTOPIC OSTEOINDUCTION BY RHBMP-2 [J].
FUJIMURA, K ;
BESSHO, K ;
KUSUMOTO, K ;
OGAWA, Y ;
IIZUKA, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 208 (01) :316-322
[10]   Cyclophosphamide diminishes inflammation and prolongs transgene expression following delivery of adenoviral vectors to mouse liver and lung [J].
Jooss, K ;
Yang, YP ;
Wilson, JM .
HUMAN GENE THERAPY, 1996, 7 (13) :1555-1566