Asymmetric expression of H19 and ADIPOQ in concave/convex paravertebral muscles is associated with severe adolescent idiopathic scoliosis

Abstract

BackgroundAdolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity. The etiology and pathology of AIS remain unexplained, and have been reported to involve a combination of genetic and epigenetic factors. Since paravertebral muscle imbalance plays an important role in the onset and progression of scoliosis, we aimed to investigate transcriptomic differences by RNA-seq and identify significantly differentially expressed transcripts in two sides of paravertebral muscle in AIS.MethodsRNA-seq was performed on 5 pairs of paravertebral muscle from 5 AIS patients. Significantly differentially expressed transcripts were validated by quantitative reverse polymerase chain reaction. Gene expression difference was correlated to clinical characteristics.ResultsWe demonstrated that ADIPOQ mRNA and H19 is significantly differentially expressed between two sides of paravertebral muscle, relatively specific in the context of AIS. Relatively low H19 and high ADIPOQ mRNA expression levels in concave-sided muscle are associated with larger spinal curve and earlier age at initiation. We identified miR-675-5p encoded by H19 as a mechanistic regulator of ADIPOQ expression in AIS. We demonstrated that significantly reduced CCCTC-binding factor (CCTF) occupancy in the imprinting control region (ICR) of the H19 gene in the concave-sided muscle contributes to down-regulated H19 expression.ConclusionsRNA-seq revealed transcriptomic differences between two sides of paravertebral muscle in AIS patients. Our findings imply that transcriptomic differences caused by epigenetic factors in affected individuals may account for the structural and functional imbalance of paravertebral muscle, which can expand our etiologic understanding of this disease.Electronic supplementary materialThe online version of this article (10.1186/s10020-018-0049-y) contains supplementary material, which is available to authorized users.

Fiber Type-Specific Morphological and Cellular Changes of Paraspinal Muscles in Patients with Severe Adolescent Idiopathic Scoliosis

“…PSM plays a significant role in spine stability and postural control, and some investigators have suggested that the muscle plays a significant role in the initiation and progression of AIS [ 2 , 8 ]. In recent decades, bilateral PSM asymmetry in AIS has been widely discussed in terms of histology [ 8 , 12 , 13 ], muscle morphology [ 2 , 11 ], molecular biology [ 7 ], and biomechanical characteristics [ 5 ]. In particular, many studies have focused on the pathological changes of muscle fiber type-specific characteristics, revealing a numerical predominance of muscle fiber type I on the convex side [ 8 , 12 , 13 ].…”

Adipocytokines: Are they the Theory of Everything?

“…Adiponectin role is the attenuation of the excessive inflammatory response in the wall of the blood vessels of the placenta through inhibition of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling (it is a protein complex that controls transcription of deoxyribonucleic acid (DNA) and cytokine production), decreasing CRP (C-reactive protein) and increasing nitric oxide [42] via activating endothelial nitric oxide synthase and inhibition of superoxide in endothelial cells [43]. Besides, adiponectin mediated the process of trophoblast invasion by modulation of MMP/TIMP (matrix metalloproteinase to tissue inhibitor of metalloproteinase) balance (this is a ratio between active extracellular [11][12][13], hyperlipidemia [22], diabetic kidney disease [30], polycystic ovary [32], ovarian cancer, gestational diabetes [39], systemic sclerosis [74], breast cancer [98], lung cancer [99], colon cancer [100], thyroid cancer [106], prostate cancer [108,109], glioblastoma [113], AIS [129], Duchene Muscular Dystrophy [132], pulmonary hypertension [149], obstructive sleep apnea [151], atherosclerosis [11], hypertension [158], preeclampsia [41][42][43][44], COVID-19 [164] Cervical & endometrial cancer [37,38], joint inflammation [64], bone erosion in rheumatoid arthritis [65], SLE with renal involvement [87] Adipsin Systemic sclerosis with PAH [83], SLE with renal involvement [ Insulin resistance &diabetes [11,…”

“…Moreover, adiponectin appears to play a role in regulating muscle mass and acts as a critical signal for muscle regeneration and suppression of proteolysis [128]. In a study of adolescent idiopathic scoliosis (AIS), a common form of spinal deformity, it was mentioned that adiponectin deficiency was involved in unequal bilateral development of the paravertebral muscles that ended in the development of lateral curvatures of the spine [129].…”

Mobile Applications for Assessing Human Posture: A Systematic Literature Review

“…(2) studies that involved the analysis of human posture deviations but considering only isolated body segment analysis such as arms and legs without spinal assessment (i.e., without evaluating spine misalignment); (3) papers that identified variations in body position regarding the balance; (4) papers with text unavailable in full; (5) papers that used mobile applications exclusively based on wearable devices.…”

“…However, due to numerous structural overloads or congenital disorders which people are subjected to, as well as age-related modifications (e.g., muscle strength reduction and reduced range of motion), many individuals develop changes in the body alignment that can culminate in severe postural deviations. These alterations have a multifactorial etiology and can also be genetic, such as adolescent idiopathic scoliosis (AIS) [5] and Hyperkyphosis [6].…”