Calcified Tissue International

, Volume 73, Issue 1, pp 49–55 | Cite as

Establishment of a Model of Cortical Bone Repair in Mice

  • T. M. Campbell
  • W. T. Wong
  • E. J. Mackie
Laboratory Investigations


A model of cortical bone repair has been established for use in mice. The cortical defect consisted of a hole drilled through the entire diameter of the tibial diaphysis. The hematoma that initially filled the drill site was invaded by cells of mesenchymal appearance within 5 days of injury. Trabeculae of mineralized woven bone were present throughout the drill site by day 9. A reaction in the periosteum adjacent to the drill site, consisting of both new bone and cartilage formation, preceded deposition of bone tissue in the drill site. New woven bone was modeled to restore the marrow cavity to normal by 4 weeks after injury, and almost normal cortical structure was achieved by 6 weeks after injury. Immunohistochemical studies indicated that type III collagen was expressed within the drill site by day 5, reached a peak at day 7, and was diminished by day 9. In contrast, type I collagen was first detectable in the drill site at day 7, and staining was more intense by day 9. Osteopontin expression in the drill site coincided with the process of mineralization of new bone in this location. The model of bone repair described here provides a method for inducing reproducible bone lesions in a readily identifiable location in mice. It will be useful in the investigation of bone cell function in mouse strains that have been subjected to genetic manipulation.


Osteoblast Osteoclast Bone repair Collagen Osteopontin 



This work was supported by the National Health and Medical Research Council of Australia, Project Grant No. 114140. The authors thank Su Toulson for excellent technical assistance.


  1. 1.
    Mackie, EJ, Tucker, RP 1999The tenascin-C knockout revisited.J Cell Sci11238473853PubMedGoogle Scholar
  2. 2.
    Strandjord, TP, Madtes, DK, Weiss, DJ, Sage, EH 1999Collagen accumulation is decreased in SPARC-null mice with bleomycin-induced pulmonary fibrosis.Am J Physiol277L628635PubMedGoogle Scholar
  3. 3.
    Yoshitake, H, Rittling, SR, Denhardt, DT, Noda, M 1999Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption.Proc Natl Acad Sci USA9681568160CrossRefPubMedGoogle Scholar
  4. 4.
    Bourque, WT, Gross, M, Hall, BK 1992A reproducible method for producing and quantifying the stages of fracture repair.Lab Anim Sci42369374PubMedGoogle Scholar
  5. 5.
    Hiltunen, A, Vuorio, E, Aro, HT 1993A standardized experimental fracture in the mouse tibia.J Orthop Res11305312PubMedGoogle Scholar
  6. 6.
    Paccione, MF, Warren, SM, Spector, JA, Greenwald, JA, Bouletreau, PJ, Longaker, MT 2001A mouse model of mandibular osteotomy healing.J Craniofac Surg12444450PubMedGoogle Scholar
  7. 7.
    Li, G, White, G, Connolly, C, Marsh, D 2002Cell proliferation and apoptosis during fracture healing.J Bone Miner Res17791799PubMedGoogle Scholar
  8. 8.
    Mackie, EJ, Ramsey, S 1996Expression of tenascin in joint-associated tissues during development and postnatal growth.J Anat188157165PubMedGoogle Scholar
  9. 9.
    Page, M, Hogg, J, Ashhurst, DE 1986The effects of mechanical stability on the macromolecules of the connective tissue matrices produced during fracture healing.I. The collagens. Histochem J18251265Google Scholar
  10. 10.
    Yamazaki, M, Nakajima, F, Ogasawara, A,  et al. 1999Spatial and temporal distribution of CD44 and osteopontin in fracture callus.J Bone Joint Surg Br81508515CrossRefPubMedGoogle Scholar
  11. 11.
    Li, X, Gu, W, Masinde, G,  et al. 2001Genetic variation in bone-regenerative capacity among inbred strains of mice.Bone29134140CrossRefPubMedGoogle Scholar
  12. 12.
    Uusitalo, H, Rantakokko, J, Ahonen, M,  et al. 2001A metaphyseal defect model of the femur for studies of murine bone healing.Bone28423429CrossRefPubMedGoogle Scholar
  13. 13.
    Eerola, I, Uusitalo, H, Aro, H, Vuorio, E 1998Production of cartilage collagens during metaphyseal bone healing in the mouse.Matrix Biol17317320CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.School of Veterinary ScienceUniversity of Melbourne, Parkville, Victoria 3010Australia

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