Discussion: Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency
In this current issue of Plastic and Reconstructive Surgery, Lyon et al. investigate the role played by osteoclasts in children with craniosynostosis by focusing on proteins known to be either osteoclastic regulators or proinflammatory. By using protein extraction techniques, they examined expression differences between fused and patent sutures in five children. Four had midline fusions (three sagittal and one metopic) and one had a lateral fusion (unilateral coronal), with ages at sampling ranging from 3 to 15 months. Three proteins—collagen 6A, fibromodulin, and adipocyte enhancer-binding protein 1—were found to be highly expressed in patent sutures, suggesting that the maintenance of an inflammatory state might be important for sutural patency. Moreover, osteomodulin, thought to be an osteoclastic-induced osteoblast maturation marker, was found to be differentially up-regulated in fused sutures. These findings led the authors to speculate that osteoclastic dysregulation might play an important role in abnormal sutural fusions. They are also appropriately restrained in not trying to draw any substantive conclusions, recognizing that their data were derived from a sampling of disparate sutures in just five patients. Probably the most important caveat to this interesting study is that their samples were taken in sutures that were already closed, in what was likely a more homeostatic state, and not during active sutural closure, a process that most probably occurred in utero. In spite of this temporal sampling challenge, disruptions in the normal balance between osteoclastic and osteoblastic activity would seem to be most likely playing some important role in the development of anomalous sutural fusions. This current study has provided us with further insights into these complex interactions. As our understanding of those genetic and biological processes underlying craniosynostosis improves, there remains the tantalizing potential that novel treatment strategies might someday come to light.