Microarray expression profiling identifies genes with altered expression in Adolescent Idiopathic Scoliosis

Abstract

Purpose Adolescent Idiopathic Scoliosis (AIS) is considered a complex genetic disease, in which malfunctioning or dysregulation of one or more genes has been proposed to be responsible for the expressed phenotype. However, to date, no disease causing genes has been identified and the pathogenesis of AIS remains unknown. The aim of this study is, therefore, to identify specific molecules with differing expression patterns in AIS compared to healthy individuals. Methods Microarray analysis and quantitative RT-PCR have examined differences in the gene transcription profile between primary osteoblasts derived from spinal vertebrae of AIS patients and those of healthy individuals. Results There are 145 genes differentially expressed in AIS osteoblasts. A drastic and significant change has been noted particularly in the expression levels of Homeobox genes (HOXB8, HOXB7, HOXA13, HOXA10), ZIC2, FAM101A, COMP and PITX1 in AIS compared to controls. Clustering analysis revealed the interaction of these genes in biological pathways crucial for bone development, in particular in the differentiation of skeletal elements and structural integrity of the vertebrae.Conclusions This study reports on the expression of molecules that have not been described previously in AIS. We also provide for the first time gene interaction pathways in AIS pathogenesis. These genes are involved in various bone regulatory and developmental pathways and many of them can be grouped into clusters to participate in a particular biological pathway. Further studies can be built on our findings to further elucidate the association between different biological pathways and the pathogenesis of AIS.

Mesenchymal Progenitors Aging Highlights a miR-196 Switch Targeting HOXB7 as Master Regulator of Proliferation and Osteogenesis

“…Our data strongly follow these observations additionally indicating that MSC‐HOXB7 have higher levels of secreted bFGF linked with a greater osteogenesis. Several evidences indicate that HOX are involved in skeletal development being also reactivated during fracture repair . Translating our findings during murine aging, we originally showed in postnatal life skeletal compartment, a progressively reduction of HOXB7 expression, suggesting that a similar dynamic may be relevant for humans (Fig.…”

Genetics and pathogenesis of idiopathic scoliosis

“…Fendri et al [82] compared mRNA expression in primary osteoblasts from vertebrae in adolescent IS patients and healthy controls and found 145 genes differentially expressed in osteoblasts. The most significant changes in expression levels were observed in homeobox genes, as well as in ZIC2, FAM101A, COMP and PITX1 .…”

“…The most significant changes in expression levels were observed in homeobox genes, as well as in ZIC2, FAM101A, COMP and PITX1 . These genes interact in the biological pathways of bone development, particularly in the differentiation of skeletal elements and the structural integrity of the vertebrae [82]. Buchan et al [83] reported rare copy number variations (CNVs) in a cohort of 143 IS patients.…”

Aberrant miR‐145–5p/β‐catenin signal impairs osteocyte function in adolescent idiopathic scoliosis

“…Recent studies have also shown lower bone mass and abnormal bone microstructure at the distal radius (6,7). Cellular studies of patients with AIS-derived primary osteoblasts have shown abnormal osteogenic differentiation ability and differentiated gene expression (8)(9)(10). Our previous study suggested fewer osteocytes in AIS bone tissues (11).…”