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Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency.
- Source :
-
Plastic and reconstructive surgery [Plast Reconstr Surg] 2018 Feb; Vol. 141 (2), pp. 250e-260e. - Publication Year :
- 2018
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Abstract
- Background: The pathophysiology of nonsyndromic craniosynostosis remains poorly understood. The authors seek to understand the cause of this condition with a specific focus on how osteoclasts may contribute to craniosynostosis. Here, the authors characterize proteins differentially expressed in patent and fused cranial sutures by comparing their respective proteomes.<br />Methods: Fused and patent suture samples were obtained from craniosynostotic patients undergoing surgery at a single academic medical center. Extracted protein from samples was interrogated using mass spectrometry. Differential protein expression was determined using maximum likelihood-based G-test with a q-value cutoffs of 0.5 after correction for multiple hypothesis testing. Immunolocalization of lead protein candidates was performed to validate proteomic findings. In addition, quantitative polymerase chain reaction analysis of corresponding gene expression of proteins of interest was performed.<br />Results: Proteins differentially expressed in patent versus fused sutures included collagen 6A1 (Col6A1), fibromodulin, periostin, aggrecan, adipocyte enhancer-binding protein 1, and osteomodulin (OMD). Maximum likelihood-based G-test suggested that Col6A1, fibromodulin, and adipocyte enhancer-binding protein 1 are highly expressed in patent sutures compared with fused sutures, whereas OMD is up-regulated in fused sutures compared with patent sutures. These results were corroborated by immunohistochemistry. Quantitative polymerase chain reaction data point to an inverse relationship in proteins of interest to RNA transcript levels, in prematurely fused and patent sutures that potentially describes a feedback loop mechanism.<br />Conclusions: Proteome analysis validated by immunohistochemistry may provide insight into the mechanism of cranial suture patency and disease from an osteoclast perspective. The authors results suggest a role of inflammatory mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of suture patency, and OMD may be involved in premature fusion. Additional validation studies are required.
- Subjects :
- Adolescent
Child
Child, Preschool
Chromatography, High Pressure Liquid methods
Collagen Type VI metabolism
Cranial Sutures physiopathology
Craniosynostoses etiology
Craniosynostoses surgery
Extracellular Matrix Proteins metabolism
Humans
Immunohistochemistry
Proteoglycans metabolism
Proteomics methods
RNA, Messenger metabolism
Real-Time Polymerase Chain Reaction
Signal Transduction
Tandem Mass Spectrometry methods
Up-Regulation
Cranial Sutures metabolism
Craniosynostoses pathology
Osteoclasts metabolism
Proteome metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-4242
- Volume :
- 141
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Plastic and reconstructive surgery
- Publication Type :
- Academic Journal
- Accession number :
- 29369995
- Full Text :
- https://doi.org/10.1097/PRS.0000000000004025