Landscape of RNAs in human lumbar disc degeneration

et al. 2017

Sci Rep

Intervertebral disc degeneration (IDD) is associated with the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. Emerging studies have shown that long noncoding RNAs (lncRNAs) play critical roles in the development of IDD. Using bioinformatics prediction, we hereby sought to identify the lncRNAs that regulate the expression of microRNA-146a-5p (miR-146a-5p), an IDD-related inflammatory factor. Our study demonstrated that lncRNA HCG18 acted as an endogenous sponge to down-regulate miR-146a-5p expression in the NP cells by directly binding to miR-146a-5p. In addition, HCG18 expression was up-regulated in the patients with IDD, bulging or herniated discs, and its level was positively correlated with the disc degeneration grade. In vitro, miR-146a-5p up-regulation HCG18 retarded the growth of NP cells by decreasing S phase of cell cycle, inducing cell apoptosis, recruitment of macrophages and hypercalcification. Conversely, down-regulation of miR-146a-5p exerted opposite effects. Furthermore, we elucidated that TRAF6, a target gene by miR-146a-5p, was modulated by HCG18 expression. Restore of TRAF6 expression by virus infection reserved the effect of HCG18 on the NP cells. Altogether, our data indicated that HCG18 suppressed the growth of NP cells and promoted the IDD development via the miR-146a-5p/TRAF6/NFκB axis.

Section: Discussionmentioning

confidence: 99%

Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR-146a-5p and regulating TRAF6 expression

Jiang

et al. 2017

Sci Rep

“…Based on the crucial role of Wnt signaling pathway in NPC senescence, nutrient deficiency, and ECM degradation, we attempted to screen for non‐coding RNAs that might be related to IDD pathogenic process and might be capable of regulating Wnt signaling. Data from GEO (GSE56081) indicate that H19 expression was significantly up‐regulated in human lumbar disc degeneration tissue samples . Moreover, H19 was found to be upregulated during osteogenesis in hMSCs; H19 significantly accelerated in vivo and in vitro osteoblast differentiation by serving as a ceRNA for miR‐141 and miR‐22 to de‐repress their shared target, β‐catenin, thus activating Wnt/β‐catenin signaling .…”

Section: Introductionmentioning

confidence: 99%

LncRNA H19 targets miR‐22 to modulate H₂O₂‐induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling

Zou

J of Cellular Biochemistry

et al. 2018

Intervertebral disc (IVD) degeneration (IDD) is a major contributor to low back pain. During IDD progression, ROS can be produced in the form of H O in nucleus pulposus cells (NPCs) in response to elevated cytokines, leading to subsequent alternations of cell fate and metabolic processes. Genetic factors are considered as main contributors to IDD pathopoiesis. Herein, we investigated the detailed function and mechanism of H19, one of the most up-regulated lncRNAs in IDD specimens, in H O -induced cell senescence model in NPCs. H19 could accelerate H O -induced degenerative changes by promoting cell senescence, increasing ADAMTS-5 and MMPs protein levels and Collagen I content, as well as suppressing NPC proliferation through activating Wnt/β-catenin signaling. Moreover, miR-22, a direct target of H19, could bind to the 3'UTR of LEF1 to inhibit its expression and reverse the effect of H19 on NPCs, thus inhibiting Wnt/β-catenin signaling. Taken together, H19 acts as a ceRNA to compete with LEF1 for miR-22, thus modulating downstream Wnt/β-catenin signaling in NPCs; H19/miR-22/LEF1 might be a novel target for improving H O -induced NPC senescence and treatment for IDD.

“…[16][17][18][19][20][21] Mounting evidence has suggested that many lncRNAs are beregulated in diverse diseases such as tumours, diabetes, coronary heart disease, osteoarthritis and also IDD. [22][23][24][25][26][27][28][29] For example, Lan and colleagues 30 profiled lncRNA expression in degenerate disc tissues and normal adults' lumbar discs by microarray and found a total of 3081 differentially expressed lncRNAs. Wang et al 31 showed that knockdown of RP11-296A18.3 suppressed human NP cell proliferation and decreased the expression of collagen I and matrix metalloproteinase (MMP)-13.…”

mentioning

confidence: 99%

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

J Cellular Molecular Medi

Peng

Gong

et al. 2018

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.