Abstract
BackgroundAlthough the pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear, there are little evidences of the pathogenesis in patients with thoracolumbar/lumbar AIS. The purpose of this study was to identify proteins or proteomes that may be causally related to the pathogenesis of AIS with structured thoracolumbar/lumbar curvature using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE).MethodsA total of 20 control volunteers and 61 AIS in patients with thoracolumbar/lumbar curvature were included. First, the plasma samples of each five AIS with pure thoracolumbar/lumbar curvature and control samples were subjected to 2D-DIGE analysis. Protein spots that were expressed differently by the AIS and control groups were selected and identified by nanoscale liquid chromatography–tandem mass spectrometry (nanoLC-MS/MS) analysis. To characterize the differently-expressed proteins in AIS patients, we performed functional pathway analysis using the Protein ANalysis THrough Evolutionary Relationships (PANTHER) system. Additionally, the proteins were compared between control and AIS using western blotting. Lastly, prospectively collected 15 control and 41 AIS with thoracolumbar/lumbar curvature samples were compared to the differentially expressed proteins.ResultsA total of 3862 ± 137 spots were detected, of which 11 spots met the criteria when compared with controls. Nine proteins were identified by nanoLC-MS/MS. Functional analysis showed the association of the proteins in AIS patients with blood coagulation using the PANTHER system. Of the proteins, vitamin D binding protein (DBP) significantly correlated with Cobb angle in thoracolumbar/lumbar curvatures. DBP expression of the prospectively collected AIS samples were significantly higher than those of controls (P < 0.05).ConclusionsThis study suggests that DBP and several coagulation-related proteins may play a role in the pathogenesis of AIS. DBP appears to be a marker of severity of AIS with thoracolumbar/lumbar curvature.
Highlights
The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear, there are little evidences of the pathogenesis in patients with thoracolumbar/lumbar AIS
Actin, fibronectin, vitamin D binding protein (DBP), coagulation factor XIII A chain, fibrinogen alpha chain, and complement factor H-related protein 1 were increased and complement C3, adiponectin, and prothrombin were decreased in AIS patients with Lenke type 5 curvature compared to controls
Of the nine over- or underexpressed proteins in AIS patients, we focused on DBP and did the following analysis because we felt it was the most significant protein and is closely related to bone metabolism
Summary
The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear, there are little evidences of the pathogenesis in patients with thoracolumbar/lumbar AIS. Adolescent idiopathic scoliosis (AIS) is a spine deformity that becomes noticeable during the pubertal growth spurt [1]. It is characterized by a 3-dimensional curvature in the absence of congenital vertebral malformation. The pathogenesis of AIS is still unclear, recent studies have suggested the role of genetic variants in bone mineralization pathways in AIS [7, 8]. These genetic variants have not been associated with clinical significance. Wang et al revealed decreased levels of the osteoblast-associated transcription factor Runx mRNA in patients with AIS [12]
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