Cellular and molecular characterization of a murine non-union model.
OBJECTIVE
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.
Department of Orthopaedic Surgery, University of California at San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143-0514, USA.
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P
Choi
C
C
Ogilvie
Z
Z
Thompson
T
T
Miclau
J A
JA
Helms
D000818:Animals; D001696:Biomechanical Phenomena; D001861:Bone Regeneration; D007150:Immunohistochemistry; D051379:Mice; D023421:Models, Animal; D019857:Osteogenesis, Distraction; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D014945:Wound Healing
D019408:Platelet Endothelial Cell Adhesion Molecule-1