Inhibition of apoptosis: a potential mechanism for syndromic craniosynostosis

The biologic pathogenesis of syndromic craniosynostosis remains unknown. The purpose of this investigation was to determine whether specific biologic differences exist between normal calvarial osteoblasts and osteoblasts derived from patients with syndromic craniosynostosis. This study (1) examined the apoptotic rate and cell cycle of osteoblasts derived from patients with syndromic craniosynostosis, and (2) investigated for the presence of soluble factors released from syndrome-derived osteoblasts. Osteoblast cell lines were established from calvarial specimens of patients with clinically diagnosed syndromic synostosis and from normal controls. A co-culture technique was used to investigate for the presence of elaborated soluble factors. Apoptotic rate and cell cycle analyses were performed by using flow cytometry after staining with annexin V-fluorescein isothiocyanate and propidiumiodide, respectively. The apoptotic rate was significantly reduced in syndrome-derived osteoblasts as compared with control osteoblasts. Control osteoblasts co-cultured with syndromic osteoblasts demonstrated a dramatic reduction in their apoptotic rate as compared with those co-cultured with control osteoblasts. These results indicate that osteoblasts derived from patients with syndromic craniosynostosis display a lower apoptotic rate, a normal DNA synthetic rate, and the capability to reduce the apoptotic rate in normal calvarial osteoblasts through the elaboration of soluble factors.