Introduction: Previously, we have demonstrated a differential dysfunction of Gicoupled receptors in osteoblasts isolated from AIS patients, leading to their stratification into three functional subgroups. Herein we examined their molecular profiles to identify the genetic causes of AIS.
Methods: Osteoblasts isolated from AIS patients were selected for each functional subgroups and compared to osteoblasts obtained from healthy matched controls. We used the latest Gene Chip human genome array Affymetrix (Human 1.0 ST array) that allow the analysis of the expression level of 38,000 well-characterized human genes. Raw data were normalized using Robust Multi-array Analysis method. Statistical analysis was performed by the EB method using FlexArray software. Selection criteria for in-depth analysis include the magnitude of change in expression (at least ±4 3-fold) and 5% false discovery rate, which represent the highest stringency selection.
Results: Among 38,000 human genes tested, only 19 genes were shared and affected to the same extent in all AIS functional subgroups. We have found 8 genes specifically associated with the functional subgroup 1; 16 gene specifically associated with the functional subgroup 2 and finally, 11 genes specifically associated with the functional subgroup 3. Most of these genes encode for regulatory proteins such as transcription factors regulating axial skeleton and somite development, signalling molecules, and extracellular matrix proteins.
Conclusion: Our data further support our functional method of stratification of AIS patients and allowed the identification of novel genes associated with either the development of a specific spinal curve pattern or more directly involved in scoliosis initiation.