BackgroundSeveral studies have described the differences in electromyographic activity and histological changes of paravertebral muscles in patients with adolescent idiopathic scoliosis (AIS). However, there is little knowledge about the muscle volumetric and fatty infiltration imbalance of patients with AIS.Material/MethodsThirty-four patients with AIS were evaluated with standardized anteroposterior (AP) and lateral standing films for the location and direction of the apex of scoliosis, coronal Cobb angle, apex vertebra translation, and thoracic kyphosis; and with magnetic resonance imaging (MRI) scan of the spine at the level of T4–L1. The muscle volume and fatty infiltration rate of bilateral deep paravertebral muscles at the level of upper end, apex, and lower end vertebra were measured.ResultsAll patients had major thoracic curve with apex of curves on the right side. The muscle volume on the convex side was larger relative to the concave side at the three levels, while the fatty infiltration rate was significantly higher on the concave side. The difference index of the muscle volume was significantly larger at the apex vertebra level than at the upper end vertebra level (p=0.002) or lower end vertebra level (p<0.001). The difference index of muscle volume correlated with apex vertebra translation (r=−0.749, p=0.032), and the difference index of fatty involution correlated with apex vertebra translation (r=0.727, p=0.041) and Cobb angle (r=0.866, p=0.005).ConclusionsOur findings demonstrated significant imbalance of muscle volume and fatty infiltration in deep paravertebral muscles of AIS patients. Moreover, these changes affected different vertebra levels, with the most imbalance of muscle volume at the apex vertebra. We interpreted this as morphological changes corresponding with known altered muscle function of AIS.

BackgroundThere is considerable discordance in the curve progression of adolescent idiopathic scoliosis (AIS) patients between monozygotic (MZ) twins, indicating that nongenetic factors must be involved in the curve progression of AIS patients. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to curve progression in AIS patients.MethodsThe genome and methylome of peripheral monocytes were compared between MZ twins discordant for curve progression. Sets of differentially methylated sites were validated using the MassARRAY platform of Sequenome on additional samples.ResultsIn the discovery study, we found evidence suggesting a lack of differences at the genome sequence level and the presence of epigenetic differences related to the curve progression of AIS patients. The top 4 differentially methylated CpG sites associated with curve severity were tested, and only site cg01374129 (CpG site located at chr8:122583383, Hg19) was confirmed in two replication cohorts. The methylation levels of site cg01374129 were significantly lower in the progression group than in the nonprogression group. Cox regression analysis demonstrated that hypo-methylation of site cg01374129 was an independent prognostic factor for curve severity. Site cg01374129 methylation as a marker achieved a sensitivity of 76.4% and a specificity of 85.6% in differentiating between samples from patients with and without curve progression (AUC = 0.827; 95% CI: 0.780 to 0.876).ConclusionIncreased curvature is associated with decreased methylation at site cg01374129. Our results indicate that methylation of site cg01374129 may therefore serve as a promising biomarker in differing between patients with and without curve progression.

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Chemotherapy is an important treatment modality for osteosarcoma. However, it often fails because of chemoresistance, especially multidrug resistance. Previously, we found several genes were involved in chemoresistance development. In this report, we used high-throughput microRNA (miRNA) expression analysis to reveal that expression of miR-140-5p was associated with chemosensitivity in osteosarcoma. The exact roles of miR-140-5p in the chemoresistance of osteosarcoma were then investigated, we found that knockdown of miR-140-5p enhanced osteosarcoma cells resistance to multiple chemotherapeutics while overexpression of miR-140-5p sensitized tumors to chemotherapy in vitro. Moreover, in vivo, knockdown of miR-140-5p also increased the osteosarcoma cells resistance to chemotherapy. Luciferase assay and Western blot analysis showed that HMGN5 was the direct target of miR-140-5p which could positively regulated autophagy. Silencing these target genes by siRNA or inhibition of autophagy sensitized osteosarcoma cells to chemotherapy. These findings suggest that a miR-140-5p/HMGN5/autophagy regulatory loop plays a critical role in chemoresistance in osteosarcoma. In conclusion, our data elucidated that miR-140-5p promoted autophagy mediated by HMGN5 and sensitized osteosarcoma cells to chemotherapy. These results suggest a potential application of miR-140-5p in overall survival, chemoresistance prognosis and treatment.