Experimental Production of Ectopic Bone

  • J. M. Connor


Ectopic osteogenesis has been the subject of intensive investigation and there are three fundamental questions to answer. What conditions can induce ectopic bone? Which cells in the soft tissues have the potential to become osteoblasts? How do these observations correlate with pathological soft tissue ossification in man? The first two questions will be considered in this chapter whilst the third is discussed in Chap. 9.


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  1. Amitani K, Nakata Y (1975) Studies on a factor responsible for new bone formation from osteosarcoma in mice. Calcif Tissue Res 17: 139–150PubMedCrossRefGoogle Scholar
  2. Amitani K, Ono K, Sakamoto Y, Nakata Y (1975) Osteogenic induction by cell-free material from murine osteosarcoma and its cultured cell line. Jpn J Cancer Res 66: 327–329Google Scholar
  3. Anderson HC (1967) Electron microscopic studies of induced cartilage development and calcification. J Cell Biol 35: 81–102PubMedCentralPubMedCrossRefGoogle Scholar
  4. Anderson HC (1976) Osteogenetic epithelial-mesenchymal cell interactions. Clin Orthop 119: 211–224PubMedGoogle Scholar
  5. Anderson HC, Coulter PR (1967) Bone formation induced in mouse thigh by cultured human cells. J Cell Biol 33: 165–177PubMedCentralPubMedCrossRefGoogle Scholar
  6. Anspach WE Jr (1964) Bone formation induced by epithelium of urinary bladder. Arch Surg 89: 446–456PubMedCrossRefGoogle Scholar
  7. Ashton BA, Allen TD, Howlett CR, Eaglesom CC, Hattori A, Owen M (1980) Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clin Orthop 151: 294–307PubMedGoogle Scholar
  8. Bang G, Johannessen JV (1972) The effect of physical treatment on the induction of heterotopic bone formation by demineralised dentin in guinea pigs. J Oral Pathol 1: 231–243PubMedCrossRefGoogle Scholar
  9. Bauer FCH, Urist MR (1981) Human osteosarcoma-derived soluble bone morphogenetic protein. Clin Orthop 154: 291–295PubMedGoogle Scholar
  10. Bell JW, Knudtson KP (1961) Soft tissue osteogenesis with gall bladder mucosal autografts. Lab Invest 10: 397–410Google Scholar
  11. Bertelsen A (1944) Experimental investigations into post-foetal osteogenesis. Acta Orthop Scand 15: 139–181CrossRefGoogle Scholar
  12. Bridges JB, Pritchard JJ (1958) Bone and cartilage induction in the rabbit. J Anat 92: 28–38PubMedCentralPubMedGoogle Scholar
  13. Buring K (1975) On the origin of cells in heterotopic bone formation. Clin Orthop 110: 293–301PubMedCrossRefGoogle Scholar
  14. Butler WT, Mikulski A, Urist MR (1977) Noncollagenous proteins of a rat dentin matrix possessing bone morphogenetic activity. J Dent Res 56: 228–232PubMedCrossRefGoogle Scholar
  15. Chalmers J, Gray DH, Rush J (1975) Observations on the induction of bone in soft tissues. J Bone Joint Surg [Br] 57: 36–45Google Scholar
  16. Desimone DP, Reddi AH (1983) The influence of vitamin A on matrix induced enchondral bone formation (in press)Google Scholar
  17. Friedenstein AJ (1968) Induction of bone tissue by transitional epithelium. Clin Orthop 59: 21–37PubMedCrossRefGoogle Scholar
  18. Friedenstein AJ (1973) Determined and inducible osteogenic precursor cells. In: Hard tissue growth, repair and remineralization. Elsevier, New York, pp 169–181 (Ciba Foundation Symposium II)Google Scholar
  19. Friedenstein AJ (1976) Precursor cells of mechanocytes. Int Rev Cytol 47: 327–359PubMedCrossRefGoogle Scholar
  20. Friedenstein AJ, Lalykina KS (1970) Lymphoid cell populations are competent systems for induced osteogenesis. Calcif Tissue Res [Suppl 4]: 105–106Google Scholar
  21. Friedenstein AJ, Lalykina KS (1972) Thymus cells are inducible to osteogenesis. Eur J Immunol 2: 602–603PubMedCrossRefGoogle Scholar
  22. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16: 381–390PubMedGoogle Scholar
  23. Friedenstein AJ, Lalykina KS, Tolmacheva AA (1967) Osteogenic activity of peritoneal fluid cells induced by transitional epithelium. Acta Anat (Basel) 68: 532–549CrossRefGoogle Scholar
  24. Gay S, Miller EJ (1978) Collagen in the physiology and pathology of connective tissue. Gustav Fischer, Stuttgart New YorkGoogle Scholar
  25. Gray DH, Speak KS (1979) The control of bone induction in soft tissues. Clin Orthop 143: 245–250PubMedGoogle Scholar
  26. Haga [], Fujimura [] (1904) Ueber Myositis ossificans traumatica (Reit- und Exercirknochen). Arch Klin Chir 72: 64–78Google Scholar
  27. Hall BK (1978) Developmental and cellular skeletal biology. Academic Press, New York San Francisco LondonGoogle Scholar
  28. Hancox NM, Wlodarski K (1972) The role of host site in bone induction by transplanted xenogenic epithelial cells. Calcif Tissue Res 8: 258–261PubMedCrossRefGoogle Scholar
  29. Hartley J, Tanz S (1951) Experimental osteogenesis in rabbit muscle. Arch Surg 63: 845–851CrossRefGoogle Scholar
  30. Heinen JH Jr, Dabbs GH, Mason HA (1949) The experimental production of ectopic cartilage and bone in the muscles of rabbits. J Bone Joint Surg [Am] 31: 765–775Google Scholar
  31. Huggins CB (1930) Influence of urinary tract mucosa on the experimental formation of bone. Proc Soc Exp Biol Med 27: 349–351CrossRefGoogle Scholar
  32. Huggins CB (1931) The formation of bone under the influence of epithelium of the urinary tract. Arch Surg 22: 377–408CrossRefGoogle Scholar
  33. Huggins CB, Sammet JF (1933) Function of the gall bladder epithelium as an osteogenic stimulus, and the physiological differentiation of connective tissue. J Exp Med 58: 393–400PubMedCentralPubMedCrossRefGoogle Scholar
  34. Huggins CB, Wiseman S, Reddi AH (1970) Transformation of fibroblasts by allogenic and xenogenic transplants of demineralised tooth and bone. J Exp Med 132: 1250–1258PubMedCentralPubMedCrossRefGoogle Scholar
  35. Ioseliani DG (1972) The use of tritiated thymidine in the study of bone induction by transitional epithelium. Clin Orthop 88: 183–196PubMedCrossRefGoogle Scholar
  36. Irving JT, LeBolt SC, Schneider EL (1981) Ectopic bone and ageing. Clin Orthop 154: 249–253PubMedGoogle Scholar
  37. Johnson FR, McMinn RMH (1956) Transitional epithelium and osteogenesis. J Anat 90: 106–116PubMedCentralPubMedGoogle Scholar
  38. Kagawa S (1965) Enzyme histochemistry of bone induction by urinary bladder epithelium. J Histochem Cytochem 13: 255–264PubMedCrossRefGoogle Scholar
  39. Koskinen EVS, Ryöppy SA, Lindholm TS (1972) Osteoinduction and osteogenesis in implants of allogenic bone matrix. Influence of somatotrophin, thyrotrophin and cortisone. Clin Orthop 87: 116–131PubMedCrossRefGoogle Scholar
  40. Lacroix P (1947) Organisers and the growth of bone. J Bone Joint Surg 29: 292–296PubMedGoogle Scholar
  41. Levander G (1938) A study of bone regeneration. Surg Gynecol Obstet 67: 705–714Google Scholar
  42. Lindholm TS, Hackman R, Lindholm RV (1973) Histodynamics of experimental heterotopic osteogenesis by transitional epithelium. Acta Chir Scand 139: 617–623PubMedGoogle Scholar
  43. Marmor L (1965) Bladder mucosa in osteogenesis. Clin Orthop 40: 82–91PubMedCrossRefGoogle Scholar
  44. Michelsson J-E, Granroth G, Andersson LC (1980) Myositis ossificans following forcible manipulation of the leg. A rabbit model for studying heterotopic bone formation. J Bone Joint Surg [Am] 62: 811–815Google Scholar
  45. Neuhof H (1917) Fascia transplantation into visceral defects. Surg Gynecol Obstet 24: 383–427Google Scholar
  46. Owen M (1970) The origin of bone cells. Int Rev Cytol 28: 213–238PubMedCrossRefGoogle Scholar
  47. Patt HM, Maloney MA (1975) Marrow regeneration after local injury. A review. Exp Hematol 3: 135–148PubMedGoogle Scholar
  48. Phemister DB (1923) Ossification in kidney stones attached to the renal pelvis. Ann Surg 78: 239–249PubMedCentralPubMedCrossRefGoogle Scholar
  49. Reddi AH, Anderson WA (1976) Collagenous bone matrix-induced enchondral ossification hemopoiesis. J Cell Biol 69: 557–572PubMedCrossRefGoogle Scholar
  50. Reddi AH, Huggins CB (1972) Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acad Sci USA 69: 1601–1605PubMedCentralPubMedCrossRefGoogle Scholar
  51. Reddi AH, Gay R, Gay S, Miller EJ (1977) Transitions in collagen types during matrix-induced cartilage, bone and bone marrow formation. Proc Natl Acad Sci USA 74: 5589–5592PubMedCentralPubMedCrossRefGoogle Scholar
  52. Salah ED, Pritchard JJ (1969) Heterotopic ossification in the tendo achules of the rat following crushing and ligation. J Anat 104: 181PubMedGoogle Scholar
  53. Severi R (1933) Produzione sperimentale di cartilagine e di osso in seguito ad iniezioni di un sale di chino. Pathologia 25: 611–619Google Scholar
  54. Takaoka K, Ono K, Amitani K, Kishimoto R, Nakata Y (1980) Solubilization and concentration of a bone-inducing substance from a murine osteosarcoma. Clin Orthop 148: 274–280PubMedGoogle Scholar
  55. Thompson J, Urist MR (1970) Influence of cortisone and calcitonin on bone morphogenesis. Clin Orthop 71: 253–270PubMedCrossRefGoogle Scholar
  56. Urist MR, Strates BS (1971) Bone morphogenetic protein. J Dent Res 50 [Suppl 6]: 1392–1406PubMedCrossRefGoogle Scholar
  57. Urist MR, Hay PH, Dubuc F, Buring K (1969) Osteogenetic competence. Clin Orthop 64: 194–220PubMedGoogle Scholar
  58. Urist MR, Jurist JM, Dubuc FL, Strates BS (1970) Quantitation of new bone formation in intramuscular implants of bone matrix in rabbits. Clin Orthop 68: 279–293PubMedCrossRefGoogle Scholar
  59. Urist MR, Mikulski AJ, Nakagawa M, Yen K (1977) A bone matrix calcification-initiator noncollagenous protein. Am J Physiol 232: C115–C127PubMedGoogle Scholar
  60. Urist MR, Nakagawa M, Nakata N, Nogami H (1978) Experimental myositis ossificans: Cartilage and bone formation in muscle in response to a diffusible bone matrix derived morphogen. Arch Pathol Lab Med 102: 312–316PubMedGoogle Scholar
  61. Urist MR, Granstein R, Nogami H, Svenson L, Murphy R (1979) Transmembrane bone morphogenesis across multiple walled diffusion chambers. New evidence for a diffusible bone morphogenetic property. Arch Surg 112: 612–619CrossRefGoogle Scholar
  62. Urist MR, Conover MA, Lietze A, Triffitt JT, Delange R (1981) Partial purification and characterization of bone morphogenetic protein. In: Cohen DV, Talmage RV, Mathews JL (eds), Proceedings of the VIIth International Conference on Calcium Regulating Hormones. Excerpta Medica, Amsterdam, pp 307–314Google Scholar
  63. Vaughan J (1981) Osteogenesis and haematopoiesis. Lancet II: 133–136CrossRefGoogle Scholar
  64. von der Mark K, von der Mark H (1977) The role of three genetically distinct collagen types in enchondral ossification and calcification of cartilage. J Bone Joint Surg [Br] 59: 458–464Google Scholar
  65. Weiss RE, Reddi AH (1980) Influence of experimental diabetes and insulin on matrix-induced cartilage and bone differentiation. Am J Physiol 238: E200–E207PubMedGoogle Scholar
  66. Weiss RE, Reddi AH (1981) Role of fibronectin in collagenous matrix-induced mesenchymal cell proliferation and differentiation in vivo. Exp Cell Res 133: 247–254PubMedCrossRefGoogle Scholar
  67. Weiss RE, Reddi AH, Nimni ME (1981) Somatostatin can locally inhibit proliferation and differentiation of cartilage and bone precursor cells. Calcif Tissue Int 33: 425–430PubMedCrossRefGoogle Scholar
  68. Wlodarski K (1969) The inductive properties of epithelial established cell lines. Exp Cell Res 57: 446–448PubMedCrossRefGoogle Scholar
  69. Wlodarski K (1978) Failure of heterotopic osteogenesis by epithelial mesenchymal cell interactions in xenogeneic transplants in the kidney. Calcif Tissue Res 25: 7–11PubMedCrossRefGoogle Scholar
  70. Wlodarski K, Hinek A, Ostrowski K (1970) Investigation on cartilage and bone induction in mice grafted with FL and WISH line human amniotic cells. Calcif Tissue Res 5: 70–79PubMedCrossRefGoogle Scholar
  71. Wlodarski K, Poltorak A, Koziorowska J (1971a) Species specificity of osteogenesis induced by WISH cell line and bone induction by Vaccinia virus transformed fibroblasts. Calcif Tissue Res 7:345–352PubMedCrossRefGoogle Scholar
  72. Wlodarski K, Poltorak A, Zaleski M, Ostrowski K (1971b) Bone induction evoked in mouse by xenogeneic grafts of the transitional epithelium. Experientia 27: 688–689PubMedCrossRefGoogle Scholar
  73. Wlodarski K, Jakobisiak M, Janowska-Wieczorek A (1980) Heterotopically induced bone marrow formation: Morphology and transplantation. Exp Hematol 8: 1016–1023PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  • J. M. Connor
    • 1
  1. 1.Duncan Guthrie Institute of Medical GeneticsYorkhill, GlasgowScotland

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