HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (28) Citing Articles via Google Scholar Google Scholar Articles by Franceschi, R.T. Search for Related Content PubMed PubMed Citation Articles by Franceschi, R.T.

Biological Approaches to Bone Regeneration by Gene Therapy

University of Michigan School of Dentistry, 1011 N. University Ave., Ann Arbor, MI 48109-1078, USA; rennyf{at}umich.edu

Safe, effective approaches for bone regeneration are needed to reverse bone loss caused by trauma, disease, and tumor resection. Unfortunately, the science of bone regeneration is still in its infancy, with all current or emerging therapies having serious limitations. Unlike current regenerative therapies that use single regenerative factors, the natural processes of bone formation and repair require the coordinated expression of many molecules, including growth factors, bone morphogenetic proteins, and specific transcription factors. As will be developed in this article, future advances in bone regeneration will likely incorporate therapies that mimic critical aspects of these natural biological processes, using the tools of gene therapy and tissue engineering. This review will summarize current knowledge related to normal bone development and fracture repair, and will describe how gene therapy, in combination with tissue engineering, may mimic critical aspects of these natural processes. Current gene therapy approaches for bone regeneration will then be summarized, including recent work where combinatorial gene therapy was used to express groups of molecules that synergistically interacted to stimulate bone regeneration. Last, proposed future directions for this field will be discussed, where regulated gene expression systems will be combined with cells seeded in precise three-dimensional configurations on synthetic scaffolds to control both temporal and spatial distribution of regenerative factors. It is the premise of this article that such approaches will eventually allow us to achieve the ultimate goal of bone tissue engineering: to reconstruct entire bones with associated joints, ligaments, or sutures. Abbreviations used: BMP, bone morphogenetic protein; FGF, fibroblast growth factor; AER, apical ectodermal ridge; ZPA, zone of polarizing activity; PZ, progress zone; SHH, sonic hedgehog; OSX, osterix transcription factor; FGFR, fibroblast growth factor receptor; PMN, polymorphonuclear neutrophil; PDGF, platelet-derived growth factor; IGF, insulin-like growth factor; TGF-ß, tumor-derived growth factor ß; CAR, coxsackievirus and adenovirus receptor; MLV, murine leukemia virus; HIV, human immunodeficiency virus; AAV, adeno-associated virus; CAT, computer-aided tomography; CMV, cytomegalovirus; GAM, gene-activated matrix; MSC, marrow stromal cell; MDSC, muscle-derived stem cell; VEGF, vascular endothelial growth factor.

KEY WORDS: adenovirus • BMP • gene expression • tissue engineering

This article has been cited by other articles:

				J.T. Koh, Z. Zhao, Z. Wang, I.S. Lewis, P.H. Krebsbach, and R.T. Franceschi Combinatorial Gene Therapy with BMP2/7 Enhances Cranial Bone Regeneration J. Dent. Res., September 1, 2008; 87(9): 845 - 849. [Abstract] [Full Text] [PDF]

				J. Chen, C. Su, Q. Lu, W. Shi, Q. Zhang, X. Wang, J. Long, Q. Yang, L. Li, X. Jia, et al. Generation of adenovirus-mediated anti-CD20 antibody and its effect on B-cell deletion in mice and nonhuman primate cynomolgus monkey Mol. Cancer Ther., June 1, 2008; 7(6): 1562 - 1568. [Abstract] [Full Text] [PDF]

				W. M. Novicoff, A. Manaswi, M. V. Hogan, S. M. Brubaker, W. M. Mihalko, and K. J. Saleh Critical Analysis of the Evidence for Current Technologies in Bone-Healing and Repair J. Bone Joint Surg. Am., February 1, 2008; 90(Supplement_1): 85 - 91. [Abstract] [Full Text] [PDF]