ABSTRACT
BACKGROUND: This study aimed to assess the role and mechanism of lncRNA NEAT1 in intervertebral disc degeneration (IVD). METHODS: LncRNA profile (GSE56081) between IVD and healthy control was downloaded from the Gene Expression Omnibus (GEO) database and analyzes differential lncRNA expression. Expression of lncRNA NEAT1 in IVD tissue and TNF-α/IL-1ß-stimulated nucleus pulposus cells were further measured by RT-PCR. The lncRNA NEAT1 overexpression plasmids (pcDNA-NEAT1) were constructed and transfected into nucleus pulposus cells. Catabolic biomarkers (MMP-3 and MMP-13), anabolic biomarkers (Col II and Aggrecan) and Nrf2 expression were further measured. To further investigate the function of Nrf2, nucleus pulposus cells were pretreated with or without 25 µM tert-Butylhydroquinone (TBHQ), a Nrf2 activator, for 18 h and subsequently cotreated with pcDNA-NEAT1. RESULTS: A total of 1432 lncRNAs were differentially expressed in GSE56081. Bioinformatic analysis found that these lncRNAs mainly enriched in Nrf2/ARE signaling pathway. LncRNA NEAT1 was highly expressed in IVD tissues than that of healthy control. Moreover, TNF-α/IL-1ß induced a time- and dose-dependent increase in the mRNA expression of lncRNA NEAT1 in the nucleus pulposus cells. Overexpression of lncRNA NEAT1 abates promotes nucleus pulposus cells proliferation but induces matrix degradation. Meanwhile, nucleus and cytoplasm Nrf2 expression was significantly down-regulated by lncRNA NEAT1 upregulation. Nrf2 activator (TBHQ) could partially reverse the inhibitory effects of overexpression of lncRNA NEAT1 on matrix degradation. CONCLUSION: Collectively, our data unveiled the lncRNA NEAT1 promotes matrix degradation by regulating Nrf2/ARE signaling pathway, suggesting a potential therapeutic for IVD in the future.
Subject(s)
Intervertebral Disc Degeneration/genetics , NF-E2-Related Factor 2/genetics , RNA, Long Noncoding/genetics , Tumor Necrosis Factor-alpha/genetics , Cell-Matrix Junctions/genetics , Humans , Hydroquinones/pharmacology , Interleukin-1beta/genetics , Intervertebral Disc Degeneration/pathology , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 3/genetics , Metabolism/genetics , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , RNA, Messenger/genetics , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: To observe the long-term efficacy and safety of warm needling therapy combined with rehabilitation training in the treatment of knee osteoarthritis (KOA) for the patients living in simple room after earthquake. METHODS: Eighty-eight cases of KOA were randomized into a warm needling group and an acupuncture group, 44 cases in each one. In the warm needling group, the warm needling therapy was applied at Neixiyan (EX LE 4) and Dubi (ST 35), in combination with rehabilitation training. In the acupuncture group, the same rehabilitation training was received, and the same acupoints were selected as the warm needling group, but only stimulated with acupuncture without moxibustion applied. The clinical efficacy was observed after 20 treatments and in 1-2 months of follow-up. RESULTS: The total effective rate was 100.0% (41/41) in the warm needling group, which was apparently superior to 85.4% (35/41) in the acupuncture group (P < 0.05). The symptom integral, pain and knee joint function score were all improved significantly after 20 treatments in both groups (all P < 0.05). The improvements in symptoms and pain in the warm needling group were superior apparently to the acupuncture group (all P < 0.05). The efficacy remained well within 2 months follow-up (all P < 0.05). But the difference in knee joint function score was not statistically significant between the two groups (all P > 0.05). CONCLUSION: The combined therapy of warm needling and rehabilitation training achieves the superior efficacy and good safety in the treatment of KOA as compared with the combined therapy of simple acupuncture and rehabilitation training for the patients living in simple room after earthquake.
