Cellular and molecular characterization of a murine non-union model

P. Choi, C. Ogilvie, Z. Thompson, T. Miclau, J. A. Helms

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Purpose. We have developed a method to study the molecular and cellular events underlying delayed skeletal repair in a model that utilizes distraction osteogenesis. Methods. The clinical states of delayed union and non-union were reproduced in this murine model by altering distraction parameters such as the inclusion and exclusion of a latency phase and variations in the rate and rhythm of distraction. Radiographic, cellular, and molecular analyses were performed on the distraction tissues. Results. Eliminating the latency period delayed bony union, but did not appreciably alter the extent of platelet endothelial cell adhesion marker (PECAM) immunostaining. Following elimination of a latency phase and a threefold increase in the rate of distraction, there was a further delay in bone regeneration and a higher rate of non-union (60%). Instead of bone, the distraction gap was comprised of adipose or fibrous tissue. Once again, despite the rigorous distraction protocol, we detected equivalent PECAM staining within the distraction gap. In a minority of cases, cartilage and osseous tissues occupied the distraction gap likely by a prolonged process of endochondral ossification. Conclusions. Here, we have altered the mechanical environment in such a way to reproducibly create delays in skeletal regeneration. These delays in skeletal tissue regeneration appear to develop even in the presence of endothelial cells, which suggests that mechanisms other than a disruption to the vascular network can account for some cases of non-union.

Original languageEnglish (US)
Pages (from-to)1100-1107
Number of pages8
JournalJournal of Orthopaedic Research
Issue number5
StatePublished - Sep 2004

Bibliographical note

Funding Information:
The authors would like to thank the following individuals for helpful suggestions in the design and execution of the experiments and critical reading of the manuscript: Celine Colnot, Diane Hu, Mark Lee, Chuanyong Lu, and Christian Puttlitz. This work was supported by funds from: NIH K08-AR02164 (T.M.), R01-AR44179 (J.A.H.), R01-AR46238 (J.A.H.).


  • Adipose
  • Delayed
  • Distraction
  • Fibrous
  • Healing
  • Non-union
  • Repair


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