Bone morphogenic protein-2 gene therapy for mandibular distraction osteogenesis

被引:81
作者
Ashinoff, RL [1 ]
Cetrulo, CL [1 ]
Galiano, RD [1 ]
Dobryansky, M [1 ]
Bhatt, KA [1 ]
Ceradini, DJ [1 ]
Michaels, J [1 ]
McCarthy, JG [1 ]
Gurtner, GC [1 ]
机构
[1] NYU, Med Ctr, Inst Reconstruct Plast Surg, Lab Microvasc Res & Vasc Tissue Engn, New York, NY 10016 USA
关键词
BMP-2; gene therapy; distraction osteogenesis;
D O I
10.1097/01.sap.0000123023.28874.1e
中图分类号
R61 [外科手术学];
学科分类号
摘要
Distraction osteogenesis (DO) requires a long consolidation period and has a low but real failure rate. Bone morphogenic proteins (BMPs) accelerate bone deposition in fractures and critical-sized bone defects, but their effects on mandibular DO are unknown. We investigated the effect of local delivery of adenovirus containing the gene for BMP-2 (Adbmp-2) on mandibular DO in a rat model. Rats (n = 54) were distracted to 3 mm over 6 days. At the start of consolidation (POD 10), Adbmp-2 or adenovirus containing the lacZ gene (AdlacZ) was injected directly into the distraction zone. After 1, 2, and 4 weeks of consolidation, mandibles were evaluated for amount of bone deposition. Adbmp-2-treated specimens demonstrated an increased amount of new bone formation by radiographic, histologic, and histomorphometric analysis. This study demonstrates that local, adenovirally-mediated delivery of BMP-2 can increase bone deposition during DO, potentially shortening consolidation and enhancing DO in poorly healing mandibles, such as occurs postirradiation.
引用
收藏
页码:585 / 591
页数:7
相关论文
共 23 条
[1]   The use of bone morphogenetic protein gene therapy in craniofacial bone repair [J].
Alden, TD ;
Beres, EJ ;
Laurent, JS ;
Engh, JA ;
Das, S ;
London, SD ;
Jane, JA ;
Hudson, SB ;
Helm, GA .
JOURNAL OF CRANIOFACIAL SURGERY, 2000, 11 (01) :24-30
[2]  
BALTZER AW, 2000, CLIN ORTHOP S, V379, pS120
[3]   Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene [J].
Baltzer, AWA ;
Lattermann, C ;
Whalen, JD ;
Wooley, P ;
Weiss, K ;
Grimm, M ;
Ghivizzani, SC ;
Robbins, PD ;
Evans, CH .
GENE THERAPY, 2000, 7 (09) :734-739
[4]   Use of bone morphogenetic protein-2 in the rabbit ulnar nonunion model [J].
Bostrom, M ;
Lane, JM ;
Tomin, E ;
Browne, M ;
Berberian, W ;
Turek, T ;
Smith, J ;
Wozney, J ;
Schildhauer, T .
CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 1996, (327) :272-282
[5]   Overview of the radiology, histology, and bone morphogenetic protein expression during distraction osteogenesis of the mandible [J].
Campisi, P ;
Hamdy, RC ;
Lauzier, D ;
Amako, M ;
Schloss, MD ;
Lessard, ML .
JOURNAL OF OTOLARYNGOLOGY, 2002, 31 (05) :281-286
[6]   Expression of bone morphogenetic proteins during mandibular distraction osteogenesis [J].
Campisi, P ;
Hamdy, RC ;
Lauzier, D ;
Amako, M ;
Rauch, F ;
Lessard, ML .
PLASTIC AND RECONSTRUCTIVE SURGERY, 2003, 111 (01) :201-208
[7]   EFFECT OF RECOMBINANT HUMAN OSTEOGENIC PROTEIN-1 ON HEALING OF SEGMENTAL DEFECTS IN NONHUMAN-PRIMATES [J].
COOK, SD ;
WOLFE, MW ;
SALKELD, SL ;
RUEGER, DC .
JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME, 1995, 77A (05) :734-750
[8]  
COOK SD, 1994, CLIN ORTHOP RELAT R, P302
[9]  
GERHART TN, 1993, CLIN ORTHOP RELAT R, P317
[10]   Ex vivo gene therapy with stromal cells transduced with a retroviral vector containing the BMP4 gene completely heals critical size calvarial defect in rats [J].
Gysin, R ;
Wergedal, JE ;
Sheng, MHC ;
Kasukawa, Y ;
Miyakoshi, N ;
Chen, ST ;
Peng, H ;
Lau, KHW ;
Mohan, S ;
Baylink, DJ .
GENE THERAPY, 2002, 9 (15) :991-999