Factors regulating endochondral ossification in spheno-occipital synchondrosis

Abstract

AIM: The spheno-occipital synchondrosis is an important growth centre of the craniofacial skeleton. It is infl uential on the position of both the maxilla and mandible. During the post-natal period, endochondral ossifi cation of the synchondrosis contributes largely to the expansion of the ossifi cation centres and growth of the cranial base. Endochondral ossifi cation plays a major role in bone formation, which can be traced by the expression of stage specifi c markers. Core binding factor alpha 1 (Cbfa1) is a key transcription factor and known to be associated with chondrocyte maturation and osteoblast differentiation. Vascular endothelial growth factor (VEGF) is a regulator of vascularization, and its maximum level of expression precedes the maximum level of new bone formation during endochondral ossifi cation in the long bone and the condyle. The factors governing growth of the synchondrosis are not fully elucidated. Whether growth of synchondrosis can be affected by mechanical stress is still unclear. It is important to understand the mechanism of Cbfa1 and VEGF underlying the development of synchondrosis, and to correlate their expressions. The aim of this study was to establish the temporal pattern of Cbfa1 and VEGF expressions in response to mechanical stress, and to correlate Cbfa1 and VEGF expression of spheno-occipital synchondrosis. MATERIALS AND METHOD: Sixty male balb/c mice were randomly divided into six experimental and six control groups corresponding to fi ve time points. The animals were sacrifi ced and cranial base synchondroses were aseptically removed. Mechanical stresses were applied on the experimental surgical explants with helical springs and incubated in organ culture for 6, 24, 48, 72 and 168 hours. Tissue sections were subjected to immunohistochemical staining for quantitative analysis of Cbfa1 and VEGF expression. RESULTS: Quantitative analysis revealed that Cbfa1 and VEGF expression reached a peak increase at 24 and 48 hours, respectively. Compared with the control groups, both Cbfa1 and VEGF were expressed consistently higher in the experimental group at all time points. CONCLUSION: Mechanical stress applied on the synchondrosis elicits Cbfa1 expression, and subsequently up-regulates the expression of VEGF. These factors act in a synchondronized manner to control the maturation of chondrocytes into hypertrophic chondrocytes and also induce chondroclast invasion and osteoblast formation, resulting in more new bone leading to growth of the spheno-occipital synchondrosis.