Cranial sutures as intramembranous bone growth sites

Intramembranous bone growth is achieved through bone formation within a periosteum or by bone formation at sutures. Sutures are formed during embryonic development at the sites of approximation of the membranous bones of the craniofacial skeleton. They serve as the major sites of bone expansion during postnatal craniofacial growth. For sutures to function as intramembranous bone growth sites, they need to remain in an unossified state, yet allow new bone to be formed at the edges of the overlapping bone fronts. This process relies on the production of sufficient new bone cells to be recruited into the bone fronts, while ensuring that the cells within the suture remain undifferentiated. Unlike endochondral growth plates, which expand through chondrocyte hypertrophy, sutures do not have intrinsic growth potential. Rather, they produce new bone at the sutural edges of the bone fronts in response to external stimuli, such as signals arising from the expanding neurocranium. This process allows growth of the cranial vault to be coordinated with growth of the neurocranium. Too little or delayed bone growth will result in wide-open fontanels and suture agenesis, whereas too much or accelerated bone growth will result in osseous obliteration of the sutures or craniosynostosis. Craniosynostosis in humans, suture fusion in animals, and induced suture obliteration in vitro has been associated with mutations or alterations in expression of several transcription factors, growth factors, and their receptors. Much of the data concerning signaling within sutures has been garnered from research on cranial sutures; hence, only the cranial sutures will be discussed in detail in this review. This review synthesizes classic descriptions of suture growth and pathology with modern molecular analysis of genetics and cell function in normal and abnormal suture morphogenesis and growth in a unifying hypothesis. At the same time, the reader is reminded of the importance of the suture as an intramembranous bone growth site.