Pathophysiology of Cranial Suture Synostosis is Expressed by Altered Temporal Sequences: 2D-Histomorphometry, Bone Mineral Density Distribution and Energy Dispersive X-ray Analysis in Normal and Pathological Immature Sutures

Introduction: In contrast to endochondral growth with ossification of a pre-existing cartilaginous matrix, cranial sutures act as intramembranous bone growth sites. New bone is produced at the sutural edges by proliferation of mesenchymal cells and subsequent differentiation into osteoblasts. The suture itself remains in an unossified stage in which maintenance of growth at the osteogenic fronts requires a balance between proliferation and differentiation. Disruption of any of these processes can result in premature fusion of calvarial sutures, known as craniosynostosis. Premature fusion of cranial sutures is a complex pathomechanism in which alterations of transcription factors, growth factors and their receptors may be the regulating items. In suture fusion type I collagen, TGF-beta, FGFR and BSP-I have been identified to be upregulated in the suture matrix, whereas CBFA1, FGF-2 and IGF-1 become expressed in the bone fronts. This process is most likely responding to external stimuli like the expanding brain. Dura mater and periosteum as well may have an influence on suture fusion and bone formation but exact signalling in normal and pathological suture fusion is still unknown. Studies on the bony structure and bony contents of normal and pathological sutures in humans were expected to give us further information about suture morphogenesis.