Coronal Suture Pathology and Synostotic Progression in Rabbits with Congenital Craniosynostosis

Abstract

The purpose of the present study was to describe coronal suture pathology and cross sectional synostotic progression in an inbred strain of rabbits with congenital craniosynostosis. Calvaria from 102 perinatal rabbits (39 unaffected; 63 bilateral or unilateral synostosis) were collected at fetal days 21 (n = 12), 25 (n = 20), 27 (n = 22), 30 (term) (n = 32), and 3 days post-term (n = 16) for gross morphologic and histologic examination. Synostotic foci, the extent of relative bony bridging, and suture morphology were evaluated qualitatively and quantitatively. Of the 204 coronal sutures examined, 91 sutures were synostosed, and 113 were patent. All synostosed sutures showed similar foci by day 25, which originated as bony bridges in the middle of each suture on the ectocortic surface. Bony bridging width increased significantly (p < .001) from day 25 through 3 days post-term, and was best described by a linear regression equation. Osteogenic front areas of synostosed sutures were up to 2.5 times greater than patent sutures in term fetuses. Findings demonstrate that coronal suture synostosis in the congenital rabbit model (1) begins early during suture morphogenesis (before 25 days of gestation); (2) consistently radiates from a single focus corresponding to a normal interdigitating region (i.e., a high-tension environment); (3) varies in onset and rate as evidenced by low R2 value between age and extent of bony bridging; and (4) is the result of early hyperostosis of the osteogenic fronts and sutural agenesis. A number of possible pathogenetic mechanisms are discussed.

Rescue of coronal suture fusion using transforming growth factor‐beta 3 (Tgf‐β3) in rabbits with delayed‐onset craniosynostosis

“…2A) at a thickness of 5-7 . The middle of each coronal suture was chosen for analysis because it is the focal point of synostosis in these rabbits (from this point, synostosis progresses in both medial and lateral directions) (Mooney et al, 1996b(Mooney et al, , 2002. Thus, this area is the most osteogenic and should be most affected by cytokine manipulation.…”

BMP-4 Response in Wild-Type and Craniosynostotic Rabbit Bone Cells

“…[7][8][9][10] Using this model, we designed the current study to begin the initial characterization of cells derived from the bone of either normal (wild-type) New Zealand White rabbits or New Zealand White rabbits with familial congenital craniosynostosis. 11 Because there is evidence of increased bone formation in craniosynostotic calvariae 11 and that bone formation can be inhibited using the bone morphogenetic protein (BMP) antagonist noggin, 12 it is logical to hypothesize that cells derived from craniosynostotic bone may be hypersensitive to stimulation by osteogenic signals. To test this hypothesis, we isolated primary bone-derived cells from 40 rabbits, stimulated them with recombinant human (rh) BMP4 or osteogenic medium, and assessed osteogenic differentiation and proliferation.…”

Comparison of Craniofacial Phenotype in Craniosynostotic Rabbits Treated with Anti–Tgf-β2 at Suturectomy Site

“…The coronal suture starts to fuse by 21 days of gestation (Mooney et al, 1996), and the anterior fontanelle and coronal suture are obliterated by 10 days of age in rabbits affected by earlyonset coronal suture fusion (Mooney et al, 1994b). A slightly elevated bony ridge along the suture and frontal "bossing" also are observed, with shortening and widening of the cranial vault.…”