Blocking bone morphogenetic protein function using in vivo noggin therapy does not rescue premature suture fusion in rabbits with delayed-onset craniosynostosis.

Abstract

BACKGROUND:

Craniosynostosis is defined as the premature fusion of one or more cranial sutures. Bone morphogenetic proteins (BMPs), regulators of ossification, have been implicated in premature suture fusion. Noggin, an extracellular BMP inhibitor, has been shown experimentally to inhibit resynostosis following surgery. The present study was designed to test the hypothesis that BMP inhibition using noggin therapy may rescue sutures destined to fuse by inhibiting initial ossification.

METHODS:

Twenty-six, 10-day old rabbits with familial, delayed-onset, coronal suture synostosis were randomly divided into three groups: (1) the sham surgical control group, (2) the bovine serum albumin-treated group [10 μg/suture (protein/vehicle controls)], and (3) the noggin therapy group (10 μg/suture; experimental group). Sutural growth was monitored by radiopaque markers implanted at 10 days of age. At 25 days, the bovine serum albumin or noggin was combined with a slow-resorbing collagen vehicle and injected subperiosteally above the coronal suture. Somatic and sutural growth data were collected at 10, 25, 42, and 84 days of age. Coronal sutures were harvested at 84 days to histologically assess fusion.

RESULTS:

Results showed no significant (p > 0.05) differences in suture separation at any age. Suture fusion assessed by histomorphology did not differ among the three groups. Although previous data showed noggin to inhibit postoperative resynostosis in this craniosynostotic rabbit model, here there was no effect on initial suture fusion.

CONCLUSION:

These results suggest that in this rabbit model of craniosynostosis, BMPs do not play a role in the pathogenesis of craniosynostosis and only play a role in postoperative bony wound healing.

• Authors: James Cray Jr, Anne M Burrows, Lisa Vecchione, John F Caccamese Jr, Joseph E Losee, Amr M Moursi, Michael I Siegel, Gregory M Cooper, Mark P Mooney
• Journal: Plastic and reconstructive surgery (Plast Reconstr Surg) Vol. 127 Issue 3 Pg. 1163-1172 (Mar 2011) ISSN: 1529-4242 [Electronic] United States
• PMID: 21364419 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Bone Morphogenetic Proteins
• Carrier Proteins
• noggin protein

Topics

• Animals
• Bone Morphogenetic Proteins (antagonists & inhibitors, physiology)
• Carrier Proteins (therapeutic use)
• Cephalometry
• Cranial Sutures (drug effects, growth & development)
• Craniosynostoses (drug therapy, pathology)
• Disease Models, Animal
• Osteogenesis (drug effects)
• Rabbits