title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Pittsburgh, Pa.; Baltimore, Md.; and New York, N.Y. From the Department of Surgery, Division of Plastic and Reconstructive Surgery, and the Departments of Anthropology, Orthodontics and Dentofacial Orthopedics, and Bioengineering, University of Pittsburgh; University of Pittsburgh and Pediatric Craniofacial Biology Laboratory, Children's Hospital of Pittsburgh, University of Pittsburgh; Department of Physical Therapy, Duquesne University; Pittsburgh Cleft-Craniofacial Research Center, Children's Hospital of Pittsburgh; Department of Oral Biology, University of Pittsburgh School of Dental Medicine; Department of Oral and Maxillofacial Surgery, University of Maryland; and Department of Pediatric Dentistry, College of Dentistry, New York University.
authors.forename: James
authors.initials: J
authors.lastname: Cray
authors.forename: Anne M
authors.initials: AM
authors.lastname: Burrows
authors.forename: Lisa
authors.initials: L
authors.lastname: Vecchione
authors.forename: John F
authors.initials: JF
authors.lastname: Caccamese
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Losee
authors.forename: Amr M
authors.initials: AM
authors.lastname: Moursi
authors.forename: Michael I
authors.initials: MI
authors.lastname: Siegel
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cooper
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mooney
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002352:Carrier Proteins / Q000627:therapeutic use*; D002508:Cephalometry; D003393:Cranial Sutures / Q000187:drug effects / Q000254:growth & development*; D003398:Craniosynostoses / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein