Proteomic Analysis of Craniosynostosis Tissue Suggests a Link Between Inflammation and Premature Suture Fusion
Sarah Lyon, BS1, Michael Januszyk, MD, PhD2, Anoop Mayampurath, PhD1, David M. Frim, MD PhD1, Darrel J. Waggoner, MD1, Tong-Chuan He, MD PhD1, Russell R. Reid, MD PhD1.
1University of Chicago, Chicago, IL, USA, 2Stanford University, Stanford, CA, USA.
Craniosynostosis is a congenital disorder associated with premature cranial suture fusion, typically resulting in craniofacial asymmetries and functional impairment. Despite its marked phenotype and relatively high prevalence, the pathobiology of this disease remains poorly understood. Here we apply proteome-wide analysis using mass spectrometry to explore the biological factors underlying premature suture fusion.
Fused and patent suture samples were obtained from five craniosynostotic patients (ages 3 to 12 months) undergoing cranioplasty at a single academic medical center in 2013 (IRB #16045B). Protein was extracted and interrogated using mass spectrometry. Differential protein expression between sample types was determined using q-value cutoffs of 0.5. Hierarchical clustering of expression data for each group was followed by canonical pathway calculations and network analysis.
Proteins significantly up-regulated in patent sutures included pro-osteogenic genes such as POSTN and OGN, as well as pro-inflammatory mediators including FMOD and multiple collagen proteins. Interestingly, osteomodulin (ODM), a key signaling molecule mediating osteoblast-osteoclast interactions in bone resorption, was significantly down-regulated in patent sutures. A super-network based on overlapping pathway topology (Figure 1) includes key osteogenic and inflammatory molecules such as TGFB and numerous interleukins.
These results suggest a potential link between an increased inflammatory response and early suture fusion. Given the wide array of anti-inflammatory agents currently available, these preliminary findings may have therapeutic implications. Additional validation studies are required.
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