title: Osteoprotegerin deficiency results in disruption of posterofrontal suture closure in mice: implications in nonsyndromic craniosynostosis.
abstract: BACKGROUND
  Little is known about the role of osteoclasts in cranial suture fusion. Osteoclasts are predominantly regulated by receptor activator of nuclear factor kappa B and receptor activator of nuclear factor kappa B ligand, both of which lead to osteoclast differentiation, activation, and survival; and osteoprotegerin, a soluble inhibitor of receptor activator of nuclear factor kappa B. The authors' work examines the role of osteoprotegerin in this process using knockout technology.
  
  
  METHODS
  Wild-type, osteoprotegerin-heterozygous, and osteoprotegerin-knockout mice were imaged by serial micro-computed tomography at 3, 5, 7, 9, and 16 weeks. Suture density measurements and craniometric analysis were performed at these same time points. Posterofrontal sutures were harvested from mice after the week-16 time point and analyzed by means of histochemistry.
  
  
  RESULTS
  Micro-computed tomographic analysis of the posterofrontal suture revealed reduced suture fusion in osteoprotegerin-knockout mice compared with wild-type and heterozygous littermates. Osteoprotegerin deficiency resulted in a statistically significant decrease in suture bone density in knockout mice. There was no reduction in the density of non-suture-containing calvarial bone between wild-type and osteoprotegerin-knockout mice. Histochemistry of suture sections supported these micro-computed tomographic findings. Finally, osteoprotegerin-knockout mice had reduced anteroposterior skull distance at all time points and an increased interorbital distance at the week-16 time point.
  
  
  CONCLUSIONS
  The authors' data suggest that perturbations in the expression of osteoprotegerin and subsequent changes in osteoclastogenesis lead to alterations in murine cranial and posterofrontal suture morphology.
authors.affiliation: Chicago, Ill. From the Section of Plastic and Reconstructive Surgery, Department of Surgery, the Laboratory of Craniofacial Biology and Development, and the Molecular Oncology Laboratory, Department of Orthopaedic Surgery, The University of Chicago Medical Center.
authors.forename: Maureen
authors.initials: M
authors.lastname: Beederman
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Kim
authors.forename: M Rose
authors.initials: MR
authors.lastname: Rogers
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Lyon
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.forename: Russell R
authors.initials: RR
authors.lastname: Reid
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003393:Cranial Sutures / Q000000981:diagnostic imaging / Q000378:metabolism; D003398:Craniosynostoses / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D005624:Frontal Bone / Q000000981:diagnostic imaging / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010010:Osteoclasts / Q000378:metabolism*; D053244:Osteoprotegerin / Q000172:deficiency* / Q000378:metabolism; D011897:Random Allocation; D012680:Sensitivity and Specificity; D020858:Tissue and Organ Harvesting; D055114:X-Ray Microtomography
chemical_list: D053244:Osteoprotegerin