BMP Antagonists Expression During Distraction Osteogenesis in a Rabbit Model

Distraction osteogenesis (DO) is a well established surgical technique for limb lengthening and replacing bone loss due to trauma, infection or malignancies. The procedure involves gradually applying controlled distraction of two bony segments post osteotomy, resulting in the generation of new bone within the distracted gap. It has previously been shown that exogenous application of BMPs can increase bone formation during DO, however exogenous BMPs have many drawbacks. An alternative method for accelerating the rate of bone formation in DO may be to modulate the BMP signaling pathway. However, the role and expression of genes in the BMP pathway during DO remains largely unknown. Study objective: to evaluate the expression of various BMP antagonists during DO in a rabbit model.

Methods: DO was applied to the right tibia of 15 skeletally mature rabbits. Distraction began after a latency period of 7 days at a rate of 0.5mm/12hrs for 3 weeks. Animals were sacrificed in groups of 2 at weekly intervals during the distraction and consolidation phase. Specimens were examined using semi-quantitative immunohistochemistry and real-time PCR. Genes examined included BMP-3; activin receptors ACVR1,2 (A,B); inhibitors nog, grem, chrd, inhibin.

Results: all of the examined genes revealed an increase in expression during the distraction phase. The most pertinent findings were increased expression of nog, chrd, and BMP-3. Almost all the genes maintained a high level of expression during consolidation. Chrd and BMP-3, however, showed a decreased expression during the consolidation phase.

Conclusion: results suggest that BMP inhibitors play a role in DO. Blocking BMP inhibitors during distraction may be an alternative method for accelerating rate of bone formation. Research was supported by the Shriners operating grant and FRSQ.