Osteogenin: Role in Bone Induction and Repair

  • A. H. Reddi
  • S. Ma
Part of the NATO ASI Series book series (NSSA, volume 184)


Bone has considerable potential for repair and regeneration. The aim of this article is to provide a concise review of bone induction. It presents the hypothesis that endogenous growth and differentiation factors isolated from bone matrix in conjunction with exogenous growth factors isolated from elsewhere will initiate and promote cartilage and bone repair. The potential for regeneration and repair of skeletal tissue is well known from the days of Hippocrates in ancient Greece. Almost a century ago Senn (1) described the utility of decalcified bone implants in the care of osteomyelitis. Pierre Lacroix (2), a Belgian orthopaedic surgeon proposed that bone may contain a substance christened “osteogenin” which may initiate bone growth. Marshall Urist (3) made the key discovery that demineralized, lyophilized bone matrix induced bone formation. Bone induction by demineralized bone matrix recapitulates the stages of long bone development (4–7).


High Performance Liquid Chromatography Bone Formation Bone Matrix Alkaline Phosphatase Activity Demineralized Bone Matrix 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    N. Senn, On the healing of aseptic bone cavities by implantation of antiseptic decalcified bone. Am. J. Med. Sci. 98: 219 (1889).CrossRefGoogle Scholar
  2. 2.
    P. Lacroix, Recent investigations on the growth of bone. Nature 156: 576 (1945).CrossRefGoogle Scholar
  3. 3.
    M. Urist, Bone formation by autoinduction. Science 150: 893 (1965).PubMedCrossRefGoogle Scholar
  4. 4.
    A.H. Reddi, Cell biology and biochemistry of endochondral bone development. Collagen Rel. Res. 1: 209 (1981).CrossRefGoogle Scholar
  5. 5.
    A.H. Reddi and C.B. Huggins, Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc. Natl. Acad. Sci. USA 69: 1601 (1972).PubMedCrossRefGoogle Scholar
  6. 6.
    A.H. Reddi and W.A. Anderson, Collagenous bone matrix-induced endochondral ossification and hemopoiesis. J. Cell Biology 69: 557 (1976).CrossRefGoogle Scholar
  7. 7.
    A.H. Reddi, Extracellular matrix and development, in “Extracellular Matrix Biochemistry,” K.A. Piez and A.H. Reddi, eds., Elsevier, New York (1984).Google Scholar
  8. 8.
    M.R. Urist, R.J. Delange and G.A.M. Finerman, Bone cell differentiation and growth factors. Science 220: 680 (1983).PubMedCrossRefGoogle Scholar
  9. 9.
    R.E. Weiss and A.H. Reddi, Synthesis and localization of fibronectin during collagenous matrix-mesenchymal cell interaction and differentiation of cartilage and bone in vivo. Proc. Natl. Acad. Sci. USA 77: 2074 (1980).PubMedCrossRefGoogle Scholar
  10. 10.
    R.E. Weiss and A.H. Reddi, Role of fibronectin in collagenous matrix-induced mesenchymal cell proliferation and differentiation in vivo. Exp. Cell Res. 133: 247 (1981).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Somerman, A.T. Hewitt, H.H. Varner, E. Schiffman, J.D. Termine, and A.H. Reddi, Identification of a bone matrix-derived chemotactic factor. Calcif. Tiss. Int. 35: 481 (1983).CrossRefGoogle Scholar
  12. 12.
    R. Landesman and A.H. Reddi, Chemotaxis of muscle-derived mesenchymal cells to bone-inductive proteins of rat. Calcif. Tiss. Int. 39: 259 (1986).CrossRefGoogle Scholar
  13. 13.
    V. Gauss-Miller, H.K. Kleinman, G.R. Martin and E. Schiffman, Role of attachment factors and attractants in fibroblast chemotaxis. J. Lab. Clin. Med. 96: 1071 (1980).Google Scholar
  14. 14.
    H. Seppa, G. Grotendorst, S. Seppa, E. Schiffman and G.R. Martin, Platelet-derived growth factor is chemotactic for fibroblasts. J. Cell Biol. 92: 584 (1980).CrossRefGoogle Scholar
  15. 15.
    N.C. Rath and A.H. Reddi, Collagenous bone matrix is a local mitogen. Nature 278: 855 (1979).PubMedCrossRefGoogle Scholar
  16. 16.
    T.K. Sampath, D.P. DeSimone and A.H. Reddi, Extracellular bone matrix-derived growth factor. Exp. Cell Res. 142: 460 (1982).PubMedCrossRefGoogle Scholar
  17. 17.
    J.R. Farley and D.J. Baylink, Purification of a skeletal growth factor from human bone. Biochemistry 21: 3502 (1982).PubMedCrossRefGoogle Scholar
  18. 18.
    S. Mohan, J.C. Jennings, T.A. Linkhart, J.F. Wergedal and D.J. Baylink, Primary structure of human skeletal growth factor (SGF): Homology with IGF-II. J. Bone Mineral Res. 3: S218 (1988).Google Scholar
  19. 19.
    E. Canalis, W.A. Peck and L.G. Raisz, Stimulation of DNA and collagen synthesis by autologous growth factor in cultured fetal rat calvaria. Science 200: 1021 (1980).CrossRefGoogle Scholar
  20. 20.
    E. Canalis, T. McCarthy and M. Centrella, A bone-derived growth factor isolated from rat calvariae is Beta-2 microglobulin. Endocrinology 121: 1198 (1987).CrossRefGoogle Scholar
  21. 21.
    P.V. Hauschka, A.E. Mavrakos, M.D. Iafrati, S.E. Doleman and M. Klagsbrun, Growth factors in bone matrix: isolation of multiple types by affinity chromatography on heparin-Sepharose. J. Biol. Chem. 261: 12665 (1986).PubMedGoogle Scholar
  22. 22.
    D. Gospodarowicz, G. Neufeld and L. Schweigerer, Fibroblast growth factor: structural and biological properties. J. Cell Physiol. Suppl. 5: 15 (1987).PubMedCrossRefGoogle Scholar
  23. 23.
    R. Ross, E.W. Raines and D.F. Bowen-Pope, The biology of platelet-derived growth factor. Cell 46: 155 (1986).PubMedCrossRefGoogle Scholar
  24. 24.
    T.K. Sampath and A.H. Reddi, Dissociative extraction and reconstitution of bone matrix components involved in local bone differentiation. Proc. Nanl. Acad. Sci. USA 78: 7599 (1981).CrossRefGoogle Scholar
  25. 25.
    T.K. Sampath and A.H. Reddi, Homology of bone inductive proteins from human, monkey, bovine and rat extracellular matrix. Proc. Natl. Acad. Sci. USA 80: 6591 (1983).PubMedCrossRefGoogle Scholar
  26. 26.
    T.K. Sampath, M. Nathanson and A.H. Reddi, In vitro trasformation of mesenchymal cells derived from embryonic muscle into cartilage in response to extracellular matrix components of bone. Proc. Natl. Acad. Sci. USA 81:3419 (1984).Google Scholar
  27. 27.
    G.T. Syftestad, J.T. Triffit, M.R. Urist and A.I. Caplan, An osteoinductive bone matrix extract stimulates the conversion of mesenchyme into chondrocytes. Calcif. Tiss. Int. 36: 625 (1984).CrossRefGoogle Scholar
  28. 28.
    A.H. Reddi, Collagenous bone matrix and gene expression in fibroblasts. in: Extracellular Matrix Influences on Gene Expression. H.C. Slavkin and R.C. Greulich, eds., Academic Press, New York (1975).Google Scholar
  29. 29.
    T.K. Sampath, N. Muthukumaran and A.H. Reddi, Isolation of osteogenin, an extracellular matrix-associated bone inductive protein by heparin affinity chromatography. Proc. Natl. Acad. Sci. USA 84: 7109 (1987).PubMedCrossRefGoogle Scholar
  30. 30.
    F.P. Luyten, N.S. Cunningham, S. Ma, N. Muthukumaran, R.G. Hammonds, W.B. Nevins, W.I. Wood and A.H. Reddi, Purification and partial amino acid sequence of osteogenin, a protein initiating bone differentiation. J. Biol. Chem. 264: 13377 (1989).PubMedGoogle Scholar
  31. 31.
    J.M. Wozney, V. Rosen, A.J. Celeste, L.M. Mitsock, M.J. Whitters, R.W. Kriz, R.M. Hewick and E.A.Wang, Novel regulators of bone formation: Molecular clones and activities. Science 242; 1528 (1988).Google Scholar
  32. 32.
    R. Howes, J.M. Bowness, G.R. Grotendorst, G.R. Martin and A.H. Reddi, Platelet-derived growth factor enhances demineralized bone matrix-induced cartilage and bone formation. Calcif. Tiss. Int. 42: 34 (1987).CrossRefGoogle Scholar
  33. 33.
    S.M. Seyedin, P. Segarini, D.M. Rosen, A.Y. Thompson, H. Bentz and J. Graycar, Cartilage-inducing factor B is a unique protein structurally and functionally related to transforming growth factor Beta. J. Biol. Chem. 262: 1946 (1987).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • A. H. Reddi
    • 1
  • S. Ma
    • 1
  1. 1.Bone Cell Biology Section National Institute of Dental ResearchNational Institutes of HealthBethesdaUSA

Personalised recommendations