Background/Aims: Congenital scoliosis (CS) is a result of anomalous development of vertebrae and is frequently associated with somitogenesis malformation. Although noncoding RNAs (ncRNAs) have been recently determined to be involved in the pathogenesis of CS, the competing endogenous RNA (ceRNA) regulatory networks in CS remain largely unknown. Methods: Sequencing was conducted to explore the ncRNA expression profiles in rat embryos (gestation day 9) following vitamin A deficiency (VAD) (n = 9 for the vitamin A deficiency-induced congenital scoliosis (VAD-CS) group and n = 4 for the control group). Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was conducted to verify the expression levels of selected mRNAs, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). Bioinformatics analysis was used to discover the possible relationships and functions of the ceRNAs. Results: A total of 749 mRNAs, 56 miRNAs, 685 lncRNAs, and 70 circRNAs were identified to have significantly different expression levels in the two groups. Wnt, PI3K-ATK, FoxO, EGFR, and mTOR were found to be the most significant pathways involved in VAD-CS pathogenesis. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of CS were built, and the gene expression mechanisms regulated by ncRNAs were unveiled via the ceRNA regulatory networks. Conclusion: We comprehensively identified ceRNA regulatory networks of embryonic somite development in VAD-CS as well as revealed the contribution of different ncRNA expression profiles. Our data demonstrate the association between mRNAs and ncRNAs in the pathogenic mechanism of CS.
Study Design. Retrospective radiographic study. Objective. To investigate the growth of the vertebrae around distal instrumented vertebra (DIV) in patients with early-onset scoliosis (EOS) who underwent dual growing rod (DGR) treatment. Summary of Background Data. Previous studies indicated that DGR was likely to preserve or even stimulate the spinal growth. However, report pertaining to the effect of growing rod on the growth of individual vertebral body is rare. Methods. The EOS patients treated with DGR who had at least four lengthenings and 5-year follow-up were enrolled. Spine radiographs at index surgery and final follow-up were reviewed. The height, width, and depth of vertebral body from DIV–2 to DIV+2, and the height of the adjacent intervertebral space (IVS) were measured. The percentage of growth was calculated. Results. Thirty-one patients (mean age, 6.2 ± 2.5 years old) met the inclusion criteria, 74.2% (23/31) of whom were female. The average follow-up was 6.2 years (range, 5.0–10.4 yr). The measured vertebrae were divided into DIV group (n = 65), DIV- group (DIV-1 and DIV-2, n = 60), and DIV+ group (DIV+1 and DIV+2, n = 47). There were 33, 90, and 78 measured IVSs in DIV, DIV–, and DIV+ group, respectively. The total percentage growth of vertebral height was significantly higher in DIV– group than that in DIV and DIV+ groups (56.6 ± 20.3% vs. 45.6 ± 18.0% and 42.7 ± 16.2%, respectively, P ≤ 0.001). The vertebrae in DIV– group also had the highest annual height growth rate (8.7 ± 2.6% vs. 7.0 ± 2.4% and 6.6 ± 2.0%, respectively, P ≤ 0.001). A significant decrease of IVS height was observed in DIV– and DIV groups (P ≤ 0.001). Conclusion. Traditional DGR with periodical distraction stimulated the longitudinal growth of the two segments immediately above DIV in patients with EOS. DGR technique had a negative effect on the development of intervertebral discs within distracted levels. Level of Evidence: 3
Congenital scoliosis (CS) is the result of anomalous vertebrae development, but the pathogenesis of CS remains unclear. Long non‐coding RNAs (lncRNAs) have been implicated in embryo development, but their role in CS remains unknown. In this study, we investigated the role and mechanisms of a specific lncRNA, SULT1C2A, in somitogenesis in a rat model of vitamin A deficiency (VAD)‐induced CS. Bioinformatics analysis and quantitative real‐time PCR (qRT‐PCR) indicated that SULT1C2A expression was down‐regulated in VAD group, accompanied by increased expression of rno‐miR‐466c‐5p but decreased expression of Foxo4 and somitogenesis‐related genes such as Pax1 , Nkx3‐2 and Sox9 on gestational day (GD) 9. Luciferase reporter and small interfering RNA (siRNA) assays showed that SULT1C2A functioned as a competing endogenous RNA to inhibit rno‐miR‐466c‐5p expression by direct binding, and rno‐miR‐466c‐5p inhibited Foxo4 expression by binding to its 3′ untranslated region (UTR). The spatiotemporal expression of SULT1C2A, rno‐miR‐466c‐5p and Foxo4 axis was dynamically altered on GDs 3, 8, 11, 15 and 21 as detected by qRT‐PCR and northern blot analyses, with parallel changes in Protein kinase B (AKT) phosphorylation and PI3K expression. Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno‐miR‐466c‐5p expression via the PI3K‐ATK signalling pathway in the rat model of VAD‐CS. Thus, SULT1C2A may be a potential target for treating CS.
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