Transforming growth factor-β isoform expression in the perisutural tissues of craniosynostotic rabbits

Objective: To describe the expression patterns of the various transforming growth factor-beta (Tgf-beta) isoforms, known to be involved in suture development, in the perisutural tissues of rabbits with naturally occurring craniosynostosis and relate such differential expression to the pathogenesis of premature suture fusion. Method. Twenty-one coronal sutures were harvested from six wild-type control New Zealand White rabbits and five rabbits with familial coronal suture synostosis at 25 days of age for histomorphometric and immunohistochemical analyses. Tgf-beta isoform immunoreactivity was assessed using indirect immunoperoxidase procedures with specific antibodies. Results: Synostosed sutures had significantly (p < .01) greater bone area and relatively more osteoblasts and osteocytes in the osteogenic fronts, compared with wild-type sutures. Tgf-beta isoform immunoreactivity showed differential staining patterns between wild-type and synostosed perisutural tissues. In wild-type sutures, Tgf-beta 1 and Tgf-beta 3 immunoreactivity was significantly (p < .001) greater than Tgf-beta2 staining in all perisutural tissues. In synostosed sutures, the opposite pattern was observed, with Tgf-beta2 immunoreactivity significantly (p < .001) greater than Tgf-beta 1 and Tgf-beta 3 in the osteogenic fronts, dura mater, and periosteum. Conclusions: Findings from this study suggest that an overexpression of Tgf-beta 2, either in isolation or in association with an underexpression of Tgf-beta 1 and Tgf-beta 3, may be related to premature suture fusion (craniosynostosis) in this pathological rabbit model. These abnormal expression patterns may be involved in premature suture fusion either through increased cell proliferation, decreased apoptosis of the osteoblasts or both at the osteogenic fronts.