Abstract
Background/Aims: LncRNAs are a new modulator in the development of intervertebral disc degeneration. However, the functional role and mechanism of HOXC13-AS in intervertebral disc degeneration remain unclear. Methods: qRT-PCR analysis was performed to measure the relative expression levels of HOXC13-AS and miR-497-5p, and the levels of IL-1β, IL-6, and TNF-α in the medium supernatant were analyzed by ELISA. The related mechanism between HOXC13-AS and miR-497-5p was detected by luciferase assays. Results: The results revealed that TNF-α and IL-1β induced HOXC13-AS expression in NP cells. HOXC13-AS was overexpressed in IDD specimens compared to control specimens, and higher expression of HOXC13-AS was correlated with high Pfirrmann scores. Ectopic expression of HOXC13-AS promoted MMP-3 and ADAMTS4 and inhibited aggrecan and collagen II expression in NP cells. Furthermore, overexpression of HOXC13-AS increased the expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Our results demonstrated that TNF-α and IL-1β induced ADAMTS5 expression and suppressed miR-497-5p expression. miR-497-5p was downregulated in IDD specimens compared to control specimens, and the lower expression of miR-497-5p was correlated with high Pfirrmann scores. The miR-497-5p level was negatively proportional to HOXC13-AS expression in IDD specimens. Luciferase analysis data indicated that ADAMTS5 was a direct target gene of miR-497-5p. HOXC13-AS induced inflammatory cytokine expression and ECM degradation by modulating miR-497-5p/ADAMTS5. Conclusion: HOXC13-AS may be a treatment target for IDD.
Highlights
Low back pain (LBP) is a common disorder that is experimentally and clinically concerning (Setton and Chen, 2004; Seguin et al, 2008; Inoue and Espinoza Orias, 2011)
We found that HOXC13-AS was overexpressed in IDD specimens compared to control specimens and that HOXC13AS induced inflammatory cytokine expression and ECM degradation
We determined that HOXC13-AS was overexpressed in IDD specimens compared to control specimens by RT-qPCR (Figure 2A)
Summary
Low back pain (LBP) is a common disorder that is experimentally and clinically concerning (Setton and Chen, 2004; Seguin et al, 2008; Inoue and Espinoza Orias, 2011). The etiology of LBP is still unclear, and the major cause of LBP is IDD (intervertebral disc degeneration) (Roughley, 2004; Raj, 2008; Loreto et al, 2011). References have noted that lncRNAs play roles in cell molecular functions such as cell differentiation, metastasis, apoptosis, and proliferation (Pan et al, 2018; Xiao et al, 2018; Xu et al, 2018; Yang et al, 2018). Gao et al (2019) noted that HOXC13-AS was upregulated in HNSC samples and that HOXC13-AS knockdown suppressed cell invasion, proliferation and invasion by modulating HMGA2/miR-3833p. The functional role and mechanism of HOXC13-AS in IDD remain unclear
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
