LncRNA-RMRP promotes nucleus pulposus cell proliferation through regulating miR-206 expression.

Long noncoding RNAs (LncRNAs) are involved in the pathogenesis of intervertebral disc degeneration (IDD). However, the biological function and expression of RMRP were still unclear. In our study, we showed that RMRP expression was up-regulated in degenerated NP tissues compared to normal NP samples, and higher RMRP expression was associated with the disc degeneration grade. Further studies indicated that ectopic expression of RMRP enhanced NP cell growth and also enhanced the expression of ki-67, PCNA and cyclin D1 in the NP cell. Moreover, overexpression of RMRP promoted the expression of Type II collagen and aggrecan and suppressed the expression of MMP13 and ADAMTS4. In addition, we found that the expression of miR-206 was down-regulated in degenerated NP tissues compared to normal NP samples, and lower miR-206 expression was correlated with the disc degeneration grade. Interestingly, we indicated that miR-206 expression in NP tissues was negatively correlated with the expression of RMRP. Ectopic expression of miR-206 suppressed NP cell proliferation and suppressed the expression of Type II collagen and aggrecan and enhanced the expression of MMP13 and ADAMTS4. Furthermore, we demonstrated that overexpression of RMRP increased NP cell growth and regulated ECM expression through targeting miR-206. These results suggested that lncRNA-RMRP promoted the progression of IDD through targeting miR-206, providing an attractive new therapeutic approach for the treatment of IDD disease.

miR-423-5p Inhibits Osteosarcoma Proliferation and Invasion Through Directly Targeting STMN1.

BACKGROUND/AIMS: Increasing evidences suggest that dysregulated expression of miRNAs contributes to the progression of various tumors. However, the underlying function of miR-423-5p in osteosarcoma remains unexplored. METHODS: The expression of miR-423-5p and STMN1 were determined in osteosarcoma samples and cell lines via quantitative real-time PCR. Colony formation and Cell Counting Kit-8 (CCK-8) assays were performed to measure cell proliferation ability and transwell analysis was used to detect cell invasion, and dual luciferase reporter assay was perform to analysis the interaction between the miR-423-5p and STMN1. RESULTS: The expression levels of miR-423-5p and STMN1 in the osteosarcoma tissues and cell lines were measured by qRT-PCR. Cell viability was determined using the clone formation and CCK-8 assays. A dual-luciferase reporter and Western blot were performed to stdudy the target gene of miR-423-5p. Here, we showed that miR-423-5p expression was downregulated in osteosarcoma tissues and cell lines. However, the expression of stathmin1 (STMN1) was downregulated in osteosarcoma tissues and cell lines. Moreover, STMN1 expression level was negatively correlated with the miR-423-5p expression in the osteosarcoma tissues. We identified STMN1 was a direct target gene of miR-423-5p in osteosarcoma cell. Overexpression of miR-423-5p inhibited osteosarcoma cell proliferation, colony formation and invasion. Furthermore, we demonstrated that STMN1 was involved in miR-423-5p-mediated cell behavior such as cell proliferation, colony formation and invasion in the osteosarcoma cell. CONCLUSION: Our present study indicated that miR-423-5p acted as a tumor suppressor gene in osteosarcoma partly through inhibiting STMN1 expression.

Emerging Roles of Long Non-Coding RNAs in Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic systemic autoimmune disease characterized by inflammation, bone erosion, spur formation of the spine and the sacroiliac joints. However, the etiology and molecular pathogenesis of AS remain largely unclear. Recently, a growing number of studies showed that long non-coding RNAs (lncRNAs) played critical roles in the development and progression of autoimmune and orthopedic conditions, including AS. Studies demonstrated that a myriad of lncRNAs (e.g. H19, MEG3, LOC645166) pertinent to regulation of inflammatory signals were deregulated in AS. A number of lncRNAs might also serve as new biomarkers for the diagnosis and predicting the outcomes of AS. In this review, we summarize lncRNA profiling studies on AS and the functional roles and mechanism of key lncRNAs relevant to AS pathogenesis. We also discuss their potential values as biomarkers and druggable targets for this potentially disabling condition.

An update on the roles of circular RNAs in spinal cord injury.

Spinal cord injury (SCI) is a disabling condition for which therapeutic options are limited. Increasing number of microarray and next-generation sequencing studies have demonstrated that SCI coincides with altered expression of circular RNAs (circRNAs) in the damaged tissue. Emerging functional evidence further pinpointed specific differentially expressed circRNAs (e.g., circ-HIPK3, cicRNA.7079, circRNA_01477, circRNA-2960, and circ_0001723) for their effects on cellular processes relevant to SCI repair and regeneration, including neuronal apoptosis, astrocyte activation, and neuroinflammation, via sponging SCI-related microRNAs. Although circRNAs and their target microRNAs appear to be good candidates for therapeutic exploitation in SCI, further investigation into the efficient delivery of these regulatory molecules in a cell-type specific manner is a pre-requisite for translating these basic discoveries into clinical benefits.

LncRNA HIF1A-AS2 promotes osteosarcoma progression by acting as a sponge of miR-129-5p.

Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play vital roles in tumor development and progression. However, the relationship between osteosarcoma and HIF1AAS2 remains unknown. The expression of HIF1AAS2 and miR-129-5p was detected in osteosarcoma cell lines and samples via qRT-PCR. Cell Counting Kit-8 (CCK-8) and invasion assays were performed to determine cell proliferation and invasion ability, and a dual luciferase reporter assay was performed to determine the interaction between HIF1AAS2 and miR-129-5p. We showed that the expression of HIF1A-AS2 was upregulated in the osteosarcoma samples compared with the expression in noncancerous samples. Moreover, patients with high HIF1A-AS2 expression had a shorter overall survival. Ectopic expression of HIF1A-AS2 enhanced osteosarcoma cell proliferation, cell cycle progression and invasion. We found that overexpression of miR-129-5p decreased the luciferase activity of wild-type (WT) HIF1A-AS2 but not mutant HIF1A-AS2. Ectopic expression of HIF1A-AS2 suppressed miR-129-5p expression in MG-63 cells. We demonstrated that miR-129-5p was downregulated in osteosarcoma and was negatively associated with HIF1A-AS2 expression. Furthermore, ectopic expression of miR-129-5p suppressed osteosarcoma cell proliferation, cell cycle progression and invasion. In addition, overexpression of HIF1A-AS2 promoted cell proliferation, cell cycle progression and invasion of osteosarcoma cells through the modulation of miR-129-5p. These results indicated that HIF1A-AS2 might be a potential therapeutic target for osteosarcoma.

MicroRNA-103 Promotes Proliferation and Inhibits Apoptosis in Spinal Osteosarcoma Cells by Targeting p57.

Osteosarcoma is one of the most aggressive malignancies with poor prognosis rates. Many studies have demonstrated that miRNAs were involved in osteosarcoma, but the role of miR-103a in osteosarcoma remains elusive. In this study, we detected the expression levels of miR-103 in osteosarcoma and non-osteosarcoma tissues and cell lines. The binding effect of miR-103 on p57 was detected by luciferase reporter assay. After altering expressions of miR-103 or p57, viability, migration, invasion, and apoptosis of MG63 cells and expressions of proteins related with the JNK/STAT and mTOR pathways were all detected. We found the higher expression of miR-103 in osteosarcoma tissues and cell lines compared with non-osteosarcoma tissues and cell lines. miR-103 overexpression promoted survival, migration, and invasion of MG63 cells. Knockdown of miR-103a inhibited cell survival, migration, and invasion by upregulating the expression of p57, which was a target of miR-103. Moreover, miR-103a overexpression activated the JNK/STAT and mTOR pathways probably through inhibiting p57 expression. In conclusion, miR-103a acted as an oncogene in osteosarcoma, probably through activating the JNK/STAT and mTOR pathways by inhibiting p57 expression.

Bipolar Sealer Device Reduces Blood Loss and Transfusion Requirements in Posterior Spinal Fusion for Degenerative Lumbar Scoliosis: A Randomized Control Trial.

STUDY DESIGN: A prospective, randomized, controlled clinical study. OBJECTIVE: To determine the efficacy of bipolar sealer device in reducing perioperative blood loss and transfusions in degenerative lumbar scoliosis patients undergoing primary posterior spinal fusion. BACKGROUND: It has recently been used successfully in pediatric spine surgery, particularly in idiopathic and neuromuscular deformities. However, there is a dearth of literature on prospective study of the efficacy of bipolar sealer device in reducing perioperative blood loss and transfusions in patients undergoing degenerative lumbar scoliosis surgery. METHODS: A total of 100 consecutive degenerative lumbar scoliosis patients who had undergone primary decompression and posterior spinal fusion with segmental spinal instrumentation between June 2010 and June 2012 were prospectively randomized into 1 of 2 groups according to whether bipolar sealer device for intraoperative/postoperative blood management was used or not. Demographic distribution, perioperative blood loss, blood transfusion rate, the length of stay, and postoperative complications were analyzed. RESULTS: The operation time was significantly shorter in the study group than in the control group, 223.4 versus 248.9 minutes (P=0.026). There was significantly lower intraoperative estimated blood loss in the bipolar sealer group, 407 versus 696 mL (P=0.000). Of the patients with the use of bipolar sealer device, the mean red blood cell transfusion requirement during hospitalization was significantly less than the control group, 0.4 versus 1.1 U/patient (P=0.003). Furthermore, significant difference existed in allogenic blood transfusion rate between the 2 cohorts. Within the study group (with the use of bipolar sealer device), the entire perioperative allogenic blood transfusion rate was 18.0% compared with 40.0% of the control group (P=0.015). There were no complications related directly to the use of the bipolar sealer. CONCLUSIONS: Utilization of a bipolar sealer during correction of lumbar degenerative scoliosis may offer comparable hemostatic effects, without prohibitive cost or adverse drug-related risks.

A meta-analysis of interlaminar minimally invasive discectomy compared to conventional microdiscectomy for lumbar disk herniation.

A meta-analysis was conducted to evaluate the evidence that compared the safety and efficacy of interlaminar minimally invasive discectomy (ILMI) and conventional microdiscectomy (MD) for treating lumbar disk herniation (LDH) patients and to develop GRADE based recommendations for using the procedures to treat LDH. Eleven studies, encompassing 1012 patients, met the inclusion criteria. Overall, the results of the meta-analysis indicated that there were significant differences between the two groups in blood loss (SMD=-0.93, 95% CI -1.84, -0.02; p=0.05), and the number of days stays in hospital (SMD=-0.79, 95% CI -1.55, -0.04; p=0.04). However, there were no significant differences in the short-term back visual analog scale (VAS) scores (SMD=-0.34, 95% CI -0.81, 0.14; p=0.16), the long-term back VAS scores (SMD=0.13, 95% CI -0.04, 0.30; p=0.14), the short-term leg VAS scores (SMD=0.14, 95% CI -0.01, 0.29; p=0.07), the long-term leg VAS scores (SMD=0.12, 95% CI -0.05, 0.30; p=0.17), the short-term Oswestry disability index (ODI) scores (SMD=0.01, 95% CI -0.14, 0.15; p=0.92), the long-term ODI scores (SMD=0.11, 95% CI -0.03, 0.25; p=0.14), and the incidence of complications (RR=1.22, 95% CI 0.88, 1.69; p=0.24). The results of this meta-analysis demonstrate that ILMI and MD are both safe and effective surgical procedures for treating LDH. Compared with MD, ILMI can shorten days in hospital, decrease the mounts of blood loss during surgery. However, the overall GRADE evidence quality was very low. Therefore, further validation is required, and medical institutions should conduct high-quality studies.