Inhibition of apoptosis: A potential mechanism for syndromic craniosynostosis

The biologic pathogenesis of syndromic craniosynostosis remains unknown. Th e purpose of this investigation was to determine whether specific biologic differences exist between normal calvarial osteoblasts and osteoblasts deri ved 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 solub le factors released from syndrome-derived osteoblasts. Osteoblast cell line s were established from calvarial specimens of patients with clinically dia gnosed syndromic synostosis and from normal controls. A co-culture techniqu e was used to investigate for the presence of elaborated soluble factors. A poptotic rate and cell cycle analyses were performed by using flow cytometr y after staining with annexin V-fluorescein isothiocyanate and propidium-io dide, respectively. The apoptotic rate was significantly reduced in syndrom e-derived osteoblasts as compared with control osteoblasts. Control osteobl asts co-cultured with syndromic osteoblasts demonstrated a dramatic reducti on in their apoptotic late 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 DN A synthetic rate, and the capability to reduce the apoptotic rate in normal calvarial osteoblasts through the elaboration of soluble factors.