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Introduction
Adolescent idiopathic scoliosis (AIS) is characterized by deformity of the spine, which develops without a known cause, predominantly in previously healthy individuals during the adolescent growth spurt (1,2). It affects between 2 and 4% of the global population, and is more prevalent in girls (gender ratio, 8:1) (3–5). Since there is currently no early preventive treatment available, and a significant proportion of patients with AIS require intensive brace therapy or invasive surgical correction (2,6,7), improved understanding regarding the etiopathogenesis of AIS is required. Several suggestions have been proposed regarding the etiology of AIS, including neuromuscular, genetic, mechanical, growth-related or developmental hypotheses; however, at present, no single key factor has been identified (8,9).
The potential role of local changes to deep paravertebral muscles in the development of AIS has been the subject of several analyses. Numerous histochemical studies have reported significant differences in fiber size and the proportion of muscle fiber types between the convex and concave sides of the scoliotic curve (10–12). Therefore, muscle imbalance and asymmetry of paravertebral muscles in patients with AIS may be considered to serve an important role in the development of spinal deformity (10–13).
The asymmetric expression of several molecules in bilateral paravertebral muscles has also been suggested to be involved in the pathogenesis of AIS. Among the various molecular hypotheses, melatonin deficiency (14,15) and dysfunctional melatonin signaling (16,17) have received major attention. The expression of melatonin receptors 1A/1B (MTNR1A/MTNR1B; also referred as MT1 and MT2 receptors) in paravertebral muscles was previously investigated by Qiu et al (18), and MTNR1B expression was shown to be asymmetric. At the protein level, Acaroglu et al (19) demonstrated an asymmetric distribution of calmodulin (CALM1) in the paravertebral muscles of patients with AIS. This finding is of particular interest, since CALM1 not only regulates the contractile properties of muscle fibers by regulating calcium transport through the cellular membranes (20), but also acts as a neurotransmitter in the regulation of melatonin secretion (21). Crosstalk between estrogens and the melatonin signaling pathway has previously been reported (22), and the existence of an anomaly specific to the estrogen system has been suggested in patients with scoliosis (23). In addition, the expression levels of estrogen receptor 2 (ESR2) have previously been investigated in the paravertebral muscles...