Evidence of in vivo osteoinduction in adult rat bone by adeno-Runx2 intra-femoral delivery.
The bone marrow microenvironment provides a unique opportunity in vivo to assess the role of genes in bone remodeling. The objective of this study was to determine whether Runx2 expression is regulated by rhBMP-2 in vivo and to examine the effect of Runx2 overexpression on bone in vivo. In the in vivo calvaria model we used, rhBMP-2 induced Runx2 protein expression in periosteal cells while in vitro, adenovirus-mediated Runx2 overexpression induced mineralization in mesenchymal stem cells. A single injection of adeno-Runx2 directly into the bone marrow of the right femur in mature rats, and subsequent analysis after 3 weeks, showed a significant bone mineral density (BMD) increase ( approximately 15%) as compared to the controls. The whole-femur mean BMD of the active virus-injected group was 0.193 (g/cm(2)) while that of the control virus-injected group was 0.175 (g/cm(2)) (P < 0.05). In addition, a significant increase (36%) in trabecular BMD at the distal end of the femur was observed. These data demonstrate that directly delivering adeno-Runx2 into bone marrow of adult rats induces osteogenesis and illustrates potential advantages of such approaches over ex vivo gene therapy protocols involving marrow cell isolation, gene transduction, and subsequent in vivo transfer.
Bhat
Bheem M
BM
Women's Health and Musculoskeletal Biology, Wyeth Research, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA. bhatb@wyeth.com
Robinson
John A
JA
Coleburn
Valerie E
VE
Zhao
Weiguang
W
Kharode
Yogendra
Y
D000256:Adenoviridae / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D015519:Bone Density; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis* / Q000235:genetics; D005269:Femur / Q000378:metabolism / Q000502:physiology*; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D012886:Skull / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta