Skip to main content
SpringerLink
Log in

Regional Gene Therapy for Hard Tissues

  • Chapter
Gene Therapy and Tissue Engineering in Orthopaedic and Sports Medicine

Part of the book series: Methods in Bioengineering ((MB))

  • 120 Accesses

Abstract

Advances in molecular biology now allow for the transfer of genes to target cells that can evoke specific biological responses with possible applications for the treatment of clinical orthopaedic problems. The purpose of this review is to discuss such potential uses of gene therapy in hard tissues, specifically in diseases related to bone and cartilage.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ala-Kokko, L., Baldwin, C.T., Moskowitz, R.W., and Prockop, D.J. 1990. Single base mutation in the type II procollagen gene (COL2A1) as a cause of primary osteoarthritis associated with a mild chondysplasia. Proc Natl Acad Sci USA 87:6567–8.

    Article  Google Scholar 

  • Arai, Y., Kubo, T., Kappei, K., Kazushige, T., Taliahaski, K., Iveda, T., Imanishik, J., Takigawa, M., and Hirasawa, Y. 1997. Adenovirus vector mediated gene transduction to chondrocytes: in vitro evaluation of therapeutic efficacy of transforming growth factor-B, and heat shock protein to gene transduction. J Rheumatol 24:1787–95.

    PubMed  CAS  Google Scholar 

  • Aspenberg, P., Thorngren, K.G., and Lomande, L.S. 1991. Dose dependent stimulation of bone induction by basic fibroblast growth factor in rats. Acta Orthop Scand 62(5):481–4.

    Article  PubMed  CAS  Google Scholar 

  • Bagi, C.M., DeLeon, E., Bommage, R., Rosen, D., and Sonner, A. 1983. Treatment of the ovariectomized rats with the complex of rhIGF-I/IGFBP-3 increases cortical and cancellous bone mass and improves structure in the femoral neck. Calcif Tissue Internat 35:578–85.

    Article  Google Scholar 

  • Baltzer, A.W.A. 1999. Bone healing by adenoviral based gene therapy with BMP-2 and TGFB [abstr]. Trans Orthop Res Soc 308.

    Google Scholar 

  • Baragi, V.M., Rehkiewicz, R.R., Jordan, H., Banadio, J., Hartman, J.W., and Roessler, B.J. 1995. Transplantation of transduced chondrocytes protects articular cartilage from interleukin-1 induced extracellular matrix degradation. J Clin Invest 96(5):2454–60.

    Article  PubMed  CAS  Google Scholar 

  • Barr, W. and Leiden, J.M. 1991. Special delivery of recombinant proteins by genetically modified myoblasts. Science 254:1507–8.

    Article  PubMed  CAS  Google Scholar 

  • Bonadio, J., Smiley, E., Patil, P., and Goldstein, S. 1999. Localized, direct plasmid gene delivery in vivo: prolonged therapy results in reproducible tissue regeneration. Nat Med 5(7):753–9.

    Article  PubMed  CAS  Google Scholar 

  • Bourque, W.T., Gross, M., and Hall, B.K. 1993. Expression of four growth factors during fracture repair. Intern Dev Biol 37(4):573–9.

    CAS  Google Scholar 

  • Brett, A.J., Haddara, W., Prevek, L., and Graham, F.L. 1994. An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3. Proc Natl Acad Sci USA 91:8802–6.

    Article  Google Scholar 

  • Brittberg, M., Lindahl, A., Ohlsson, C., Isahsson, O., and Peterson, L. 1994. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–95.

    Article  PubMed  CAS  Google Scholar 

  • Bruder, S., Kraus, K.H., Goldberg, V.M., and Kadiyala, S. 1998. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. J Bone Joint Surg 80A:985–96.

    Google Scholar 

  • Canalis, E., Centrella, M., Burch, W., and McCarthy, T.L. 1989. Insulin-like growth factor 1 mediates selective anabolic effects of parathyroid hormone in bone cultures. J Clin Invest 83:60–5.

    Article  PubMed  CAS  Google Scholar 

  • Canalis, E. and Lian, J.B. 1988. Effects of bone associated growth factors on DNA, collagen and osteocalcin synthesis in cultured fetal rat calvariae. Bone 9:243–6.

    Article  PubMed  CAS  Google Scholar 

  • Canalis, E., McCarthy, T.L., and Centrella, M. 1989. The regulation of bone formation by local growth factors. J Bone Mineral Res 6:27–56.

    Google Scholar 

  • Centrella, M., Horowitz, M.C., Wozney, J.M., and McCarthy, T.L. 1994. Transforming growth factor beta-gene family member and bone. Endocrine Rev 15: 27–39.

    CAS  Google Scholar 

  • Cook, S.D., Baffes, G.C., Wolfe, M.W., Sampath, T.K., Rueger, D.C., and Whitecloud, T.S. 1994a. The effect of recombinant human osteogenic protein-1 on healing of large segmental bone defects. J Bone Joint Surg 76-A:827–38.

    Google Scholar 

  • Cook, S.D., Baffes, G.C., Wolfe, M.W., Sampath, T.K., and Rueger, D.C. 1994b. Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model. Clin Orthop 301:302–12.

    Google Scholar 

  • Cook, S.D., Wolfe, M.W., Salkeld, S.L., and Rueger, D.C. 1995. Effect of recombinant human osteogenic protein-1 on healing of segmental defects in nonhuman primates. J Bone Joint Surg 77-A:734–50.

    Google Scholar 

  • Crystal, R.G. 1995. Transfer of genes to humans: early lessons and obstacles to success. Science 404–10.

    Google Scholar 

  • Dai, Y., Reiman, M., Naviaux, R.K., and Verma, I.M. 1992. Gene therapy via primary myoblasts: long term expression of Factor IX protein following transplantation in vivo. Proc Natl Acad Sci USA 89:10892–5.

    Article  PubMed  CAS  Google Scholar 

  • Ebeling, P.R., Jones, J.D., O’Fallon, W.M., Janes, C.L., and Riggs, B.L. 1993. Short-term effects of recombinant human insulin-like growth factor 1 on bone turnover in normal women. J Clin Endocrinol Metab 77:1384–7.

    Article  PubMed  CAS  Google Scholar 

  • Engstrand, T., Daluiski, A., Finerman, G.A.M., and Lieberman, J.R. 1998. Enhanced chondrocytes overexpressing growth factor TGF-B. Trans Orthop Orth Res Soc 23:998.

    Google Scholar 

  • Evans, C.H. and Robbins, P.D. 1995. Possible orthopaedic applications of gene therapy. J Bone Joint Surg 77A:1103–14.

    Google Scholar 

  • Fang, J., Zhu, Y.Y., Smiley, E., Bonadio, J., Rouleau, J.P., Goldstein, S.A., McCauley, L.K., Davidson, B.L., and Roessler, B.J. 1996. Stimulation of new bone formation by direct transfer of osteogenic plasmid genes. Proc Natl Acad Sci USA 93:5753–8.

    Article  PubMed  CAS  Google Scholar 

  • Fortier, L.A., Lust, G., Mohammed, H.O., and Nixon, A.J. 1999. Coordinate upreg-ulation of cartilage matrix synthesis in fibrin cultures supplemented with exogenous insulin-like growth factor-1. J Orthop Res 17:467–74.

    Article  PubMed  CAS  Google Scholar 

  • Galera, P., Redini, F., Vivien, D., Bonaventure, J., Penfornis, H., Loyau, G., and Pujol, J.P. 1992. Effects of transforming growth factor-b1 (TGF-b1) on matrix synthesis by monolayer cultures of rabbit articular chondrocytes during the dedifferentiating process. Exp Cell Res 200:379–92.

    Article  PubMed  CAS  Google Scholar 

  • Galera, P., Vivien, D., Pronost, S., Bonaventure, J., Redini, F., Loyau, G., and Pujol, J.P. 1992. Transforming growth factor-beta 1 up regulation of collagen type II in primary cultures of rabbit articular chondrocytes involves increased mRNA levels without affecting mRNA stability and procollagen processing. J Cell Physiol 153:596–606.

    Article  PubMed  CAS  Google Scholar 

  • Gerhart, T.N., Kirker-Head, C.A., Kriz, J.J., Holtrop, M.E., Hennig, G.E., Hipp, J., Schelling, S.H., and Wang, E. 1993. Healing segmental femoral defects in sheep using recombinant human bone morphogenetic protein. Clin Orthop 293: 317–26.

    PubMed  Google Scholar 

  • Gomez-Foix, A.M., Coats, W.S., Baques, S., Alam, T., Gerard, R.D., and Newgard, C.B. 1992. Adenovirus mediate transfer of the muscle glycogen Phosphorylase gene into hepatocytes confers altered regulation of glycogen metabolism. J Biol Chem 267:25129.

    PubMed  CAS  Google Scholar 

  • Graves, D.T., Valentin-Opran, A., Delgado, R., Valente, A.J., Mundy, G., and Pichie, J. 1989. The potential role of platelet derived growth factor as an autocrine or paracrine factor for human bone cells. Connect Tissue Res 23:209–18.

    Article  PubMed  CAS  Google Scholar 

  • Jones, N. and Shenk, T. 1979. Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell 17:683.

    Article  PubMed  CAS  Google Scholar 

  • Joyce, M.C., Jingushi, S., and Bolander, M.C. 1990. Transforming growth factors-B in the regulation of fracture repair. Orthop Clin No Am 21:199–209.

    CAS  Google Scholar 

  • Kawaguchi, H., Kurokawa, T., Hanada, K., Aiyaman, Y., Tamira, M., Ogata, E., and Matsumoto, T. 1994. Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin diabetic rats. Endocrinology 135:774–81.

    Article  PubMed  CAS  Google Scholar 

  • Lieberman, J.R., Daluiski, A., Stevenson, S., McAllister, P., Lee, Y., Wu, L., Kabo, J.M., Finerman, G.A.M., and Witte, O.N. 1999. Regional gene therapy with BMP producing bone marrow cells heals segmental femoral defects in rats. J Bone Joint Surg 81A:905–17.

    Google Scholar 

  • Lieberman, J.R., Le, L., Wu, L., Finerman, G.A.M., Berk, A.J., Witte, O.N., and Stevenson, S. 1998. Regional gene therapy with a BMP-2 producing cell murine stromal cell line induces heterotopic and orthotopic bone formation in rodents. J Orthop Res 16:330–9.

    Article  PubMed  CAS  Google Scholar 

  • Linkhart, T.A., Mohan, S., and Baylink, D.J. 1996. Growth factors for bone growth and repair: IGF, TGF-B and BMP. Bone 19(1 Suppl):IS-12S.

    Article  Google Scholar 

  • Menche, D.S., Vangsness, C.T., Pitman, M., Gross, A.E., and Peterson, L. 1998. The treatment of isolated articular cartilage lesions in the young individual. Instr Course Lect American Academy of Orthopaedic Surgeons 47:505–15.

    CAS  Google Scholar 

  • Mitani, K., Graham, F.L., and Caskey, C.T. 1994. Transduction of human bone marrow by adenoviral vector. Hum Gene Ther 5:941–8.

    Article  PubMed  CAS  Google Scholar 

  • Mitani, K., Graham, F.L., Caskey, C.T., and Kochanek, S.T. 1995. Rescue, propagation and partial purification of a helper virus dependent adenovirus vector. Proc Natl Acad Sci USA 92:3854–8.

    Article  PubMed  CAS  Google Scholar 

  • Morsy, M.A., Gu, M.C., Motzel, S., Zhao, J., Lin, J., Su, Q., Allen, H., Franklin, L., Parks, R.J., Grahem, F.L., Kochanek, S., Brett, A.J., and Caskey, C.T. 1998. An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene. Proc Natl Acad Sci USA 95:7866–71.

    Article  PubMed  CAS  Google Scholar 

  • Mundy, G.L. 1997. Growth factors as potential therapeutic agents in osteoporosis. Instr Course Lect American Academy of Orthopaedic Surgeons 46:495–8.

    CAS  Google Scholar 

  • Nixon, A.J., Fortier, L.A., Williams, J., and Mohammed, H.O. 1999. Enhanced repair of extensive articular defects by insulin-like growth factor-1 ladlin fibrin composites. J Orthop Res 17:475–87.

    Article  PubMed  CAS  Google Scholar 

  • Praemer, A., Furner, S., and Rice, D.P. 1992. Musculoskeletal Conditions in the United States. 83–124, Park Ridge, IL: American Academy of Orthopaedic Surgeons.

    Google Scholar 

  • Prockop, D.J. 1997. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–4.

    Article  PubMed  CAS  Google Scholar 

  • Riley, E.H., Lane, J.M., Urist, M.R., Lyons, K.M., and Lieberman, J.R. 1996. Bone morphogenetic protein-2. Biology and applications. Clin Orthop 324:39–46.

    Article  PubMed  Google Scholar 

  • Roessler, B.J., Allen, E.D., Wilson, J.M., Hartman, J.W., and Davidson, B.L. 1993. Adenoviral mediated gene transfer to rabbit synovium in vivo. J Clin Invest 92:1085–92.

    Article  PubMed  CAS  Google Scholar 

  • Rosen, V. and Thies, R.S. 1992. The BMP proteins in bone formation and repair. Trends Gen 8(3):97–102.

    Article  CAS  Google Scholar 

  • Rosenfeld, M.A., Yoshimura, K., Trapnell, B.C., Yoneyama, K., Rosenthal, E.R., Dalemans, W.M., Fukayama, J., Bargon, L.E., Stier, L., Stratford-Perricaudet, M., Guggino, W.B., Pavirani, A., Lecocq, J.P., and Crystal, R.G. 1992. In vivo transfer of the human cystic fibrosis transmembrane conductane gene to the airway epithelium. Cell 68:143–55.

    Article  PubMed  CAS  Google Scholar 

  • Sandberg, M.M., Aro, H.T., and Vuorio, E.I. 1993. Gene expression during bone repair. Clin Orthop 289:292–312.

    PubMed  Google Scholar 

  • Scaduto, A.A. and Lieberman, J.R. 1999. Gene therapy for osteoinduction. Orthop Clin No Am 30(4):625–33.

    Article  CAS  Google Scholar 

  • Schwarz, E.M. (In press). The adeno-associated virus vector for orthopaedic gene therapy. Clin Orthop.

    Google Scholar 

  • Sellers, R.S., Peluso, D., and Morris, E.A. 1997. The effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the healing of full thickness defects of articular cartilage. J Bone Joint Surg 79A:1452–69.

    Google Scholar 

  • Setoguchi, Y., Jaffe, H.A., Danel, C., and Crystal, R.G. 1994. Ex vivo and in vivo gene transfer to the skin using replication deficient adenovirus vectors. J Invest Dermatol 102:415–21.

    Article  PubMed  CAS  Google Scholar 

  • Thaller, S.R., Dart, A., and Tesluk, H. 1993. The effects of insulin-like growth factor on critical size calvarial defects in Sprague-Dawley rats. Ann Plast Surg 31:429–33.

    Article  PubMed  CAS  Google Scholar 

  • Tornita, T., Hashimoto, H., Tomita, N., Morishita, R., Lee, S.B., Hayashida, K., Nakamura, N., Yonenubo, K., Kaneda, Y., and Ochi, T. 1997. In vivo direct gene transfer into articular cartilage by intraarticular injection mediated by HVJ (Sender virus) and liposomes. Arthritis Rheum 40:901–6.

    Article  Google Scholar 

  • Urist, M.R. 1965. Bone formation by autoinduction. Science 150:893–9.

    Article  PubMed  CAS  Google Scholar 

  • Wakitani, S., Goto, T., Pineda, S.J., Young, R.G., Mansour, J.M., Caplan, A.I., and Goldberg, V.M. 1994. Mesenchymal cell based repair of large, full thickness defects of articular cartilage. J Bone Joint Surg 76A:579–92.

    Google Scholar 

  • Wang, E.A., Rosen, V., D’Alessandro, J.S., Bauduy, M., Cordes, P., Harada, T., Israel, P.I., Hewick, R.M., Kerns, K.M., LaPan, P., Luxenberg, D.P., McQuaid, D., Martsatsos, I.K., Nove, J., and Wozney, J.M. 1990. Recombinant human bone morphogenetic protein induces formation. Proc Natl Acad Sci USA 87:2220–4.

    Article  PubMed  CAS  Google Scholar 

  • Werntz, J.R., Lane, J.M., Burstein, A.H., Justin, R., Klein, R., and Tomin, E. 1996. Qualitative and quantitative analysis of orthopaedic bone regeneration by marrow. J Orthop Res 14:85–93.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J.M. 1995. Gene therapy for cystic fibrosis: challenges and future directions. J Clin Invest 96:2547–754.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J.M. 1996. Adenoviruses as gene delivery vehicles. N Engl J Med 1185–7.

    Google Scholar 

  • Wozney, J.M., Rosen, V., Celeste, A.J., Mitsock, L.M., Whitters, J.J., Kriz, R.W., Hewick, R.M., and Wang, E.A. 1988. Novel regulators of bone formation: molecular clones and activities. Science 1528–34.

    Google Scholar 

  • Yasko, A.W., Lane, J.M., Fellinger, E.J., Rosen, V., Wozney, J.M., and Wang, E.A. 1992. The healing of segmental bone defects induced by recombinant human bone morphogenetic protein (rhBMP-2): a radiographic, histological, and biomechanical study in rats. J Bone Joint Surg 74A:659–70.

    Google Scholar 

Download references

Authors
  1. Jay R. Lieberman
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Growth and Development Laboratory Department of Orthopaedic Surgery and Molecular Genetics and Biochemistry, Chilren’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, PA, 15213-2583, USA

    Johnny Huard

  2. Department of Orthopaedic Surgery Musculoskeletal Research Center Center for Sports Medicine, University of Pittsburgh, Pittsburgh, PA, 15213-2583, USA

    Freddie H. Fu

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Birkhäuser Boston

About this chapter

Cite this chapter

Lieberman, J.R. (2000). Regional Gene Therapy for Hard Tissues. In: Huard, J., Fu, F.H. (eds) Gene Therapy and Tissue Engineering in Orthopaedic and Sports Medicine. Methods in Bioengineering. Birkhäuser Boston. https://doi.org/10.1007/978-1-4612-2126-5_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-2126-5_3

  • Publisher Name: Birkhäuser Boston

  • Print ISBN: 978-1-4612-7424-7

  • Online ISBN: 978-1-4612-2126-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation