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Effects of a Noggin Therapy on Craniofacial Growth and Development in a Rabbit Model with Craniosynostosis
James Cray Jr., Ph.D., Annie M. Burrows, Ph.D., Lisa Vecchione, D.M.D., Amr Moursi, D.D.S., Ph.D., Joseph E. Losee, M.D., Gregory M. Cooper, Ph.D., and Mark P. Mooney, Ph.D.
Pediatric Craniofacial Biology Laboratory
Department of Surgery
University of Pittsburgh
Division
2010-03-29
Presenter: Dr. James Cray Jr., Ph.D.
Affidavit:
Director Name:
Author Category: Resident/Fellow
Presentation Category: Basic Science Research
Abstract Category: Craniomaxillofacial
Craniosynostosis (CS) is defined as the premature fusion of one or more cranial sutures. Bone morphogenetic protein (BMP) signaling has been implicated in osteogenesis and faulty regulation can cause hyper-ossification. Noggin, a BMP inhibitor, has been shown to inhibit resynostosis following surgery to correct a primary synostosis in a CS rabbit model. The present study was designed to determine the effects of adding Noggin to a suture undergoing pathological fusion. Twenty-nine CS rabbits were assigned to: 1) sham controls, 2) bovine serum albumin (BSA) controls, or 3) Noggin therapy (15 mg) experimental group. At 10 days of age, radiopaque markers were implanted in rabbits on either side of the coronal suture to monitor sutural growth. At 25 days of age, BSA or Noggin was combined with a slow-resorbing collagen vehicle and injected subperiosteally above the coronal suture. Cephalometric data was collected for 10, 25, 42, and 84 days of age, and histomorphometry was conducted after suture harvest at 84 days to assess suture fusion. Results suggest Noggin therapy had no effect on bone separation at the coronal suture, no effect on delaying the fusion of the suture, and no effect on craniofacial growth. Although Noggin was an important inhibitor in post-operative resynostosis after surgical extirpation of a suture in the CS rabbit model, Noggin had no effect on growth when added directly to the fusing suture. The results suggest BMP may have a limited role within the suture local environment, and BMP inhibition does not directly influence suture fusion.
