Gene Expression Profiles Induced by Growth Factors in In Vitro Cultured Myocytes

Disruption in the normal adolescent growth spurt can cause the spinal deformities that result in idiopathic scoliosis. It is defined by the presence of lateral deformity of the spine, with otherwise normal vertebrate bodies and without other diagnoses. Due to its prevalence of 2%3% in school-aged children it poses a considerable health burden in the pediatric population. In general, spinal curvatures can be classified into congenital, neuromuscular, and the idiopathic forms [1,2]. Congenital forms of scoliosis involve structural malformations of the spine that are visible on radiographs and include segmental abnormalities such as hemivertebrae, wedge-shaped vertebrae, vertebral fusions and bars. In contrast to most idiopathic forms of scoliosis, congenital forms are resistant to correction and frequently progress to cause severe deformation, thus pose the most clinical problems [3]. In line with the segmental patterning that leads to the formation of the spine, four mutations associated with congenital scoliosis have been found in genes associated with the human segmentation clock mechanism (DLL3, MESP2, LFNG, HES7) [4]. Genome-wide association studies have been performed for families with idiopathic scoliosis and have identified polymorphisms in one gene (CHD7) that regulates multiple genetic pathways [5]. This implies that variations in other genes responsible for rare disorders may likewise contribute to idiopathic scoliosis. This notion has been contended before [6] arguing that so-called “idiopathic” scoliosis may be the result of sub-clinical lower motor neuron disorder. Histochemical studies of the thoracic part of the erector spinae muscles in scoliosis have shown consistently a changed fiber structure on the convex versus the concave side of the spine. Thus, this deviation in adult onset idiopathic scoliosis also may constitute one of the primary factors in the pathogenesis of the spinal curvature [7-9], but controversies still exist [10]. In any case, the formation of contractile myofibrils requires the ordered stepwise onset of expression of muscle specific proteins. Any defects in the expression patterns of muscle-specific genes may underlie muscle disorders [11] and, consequently, congenital or idiopathic disorders of the human skeletal apparatus including scoliosis. Changes in mRNA levels have been shown to be the primary genetic defects in muscular dystrophies, including mRNA for embryonic myosin heavy chain, α-cardiac actin, versican, acetylcholine receptor α-1, thrombospondin 4 and others [12]. Further, a heterozygous missense mutation in the MEGF10 gene was found to impair the regeneration of adult muscle in response to injury or disease and leads to myopathy and scoliosis [13]. Minor defects in muscle-specific genes might thus instigate adolescentonset idiopathic scoliosis due to altered responses to a changed growth factor environment during Research Article