Abstract
The excessive apoptosis of nucleus pulposus (NP) cells is a major risk factor in the progress of cervical intervertebral disc degeneration (IVDD). In this study, we investigated the impact of miR-98 on apoptosis of NP cells and the potential molecular mechanisms. Lipopolysaccharide (LPS) was used to establish an NP cell IVDD model. The sponging effect of miR-98 on TRAIL 3′UTR was predicted by ENCORI and assessed by the dual-luciferase reporter gene system. The expression levels of miR-98, TRAIL, and TRAIL pathway-related genes were tested by qRT-PCR, Western blot, and immunofluorescence analysis. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell viability was analyzed by MTT assay. It was found that the expression level of miR-98 was downregulated, while the level of TRAIL was upregulated in IVDD tissues, and their levels were negatively and positively associated with the clinical MRI grade, respectively. The LPS treatment resulted in a significant decrease of the miR-98 expression level and an increase of the TRAIL expression level in NP cells. miR-98 reduced NP cell apoptosis under LPS treatment in vitro. miR-98 directly targeted TRAIL. Moreover, the mRNA and protein levels of DR5, FADD, cleaved caspase8, cleaved caspase3, and cleaved PARP were downregulated by miR-98 overexpression. Overexpression of TRAIL partially reversed the suppressive roles of miR-98 on cell apoptosis and activation of the TRAIL pathway. We concluded that miR-98 inhibited apoptosis of NP cells by inactivating the TRAIL pathway via targeting TRAIL in IVDD NP cells. These results indicated that miR-98 might be a therapeutic target for IVDD.
Highlights
Cervical intervertebral disc degeneration (IVDD) is a common clinical disease, and it affects more than 62% of patients whose age was over 40 years, with or without any clinical symptom [1]
Accumulating evidence indicates that the levels of miRNAs are frequently dysregulated in intervertebral disc degeneration, which can induce nucleus pulposus (NP) cell apoptosis and destroy the balance of cellmatrix synthesis and degradation [7,8,9], for instance, Sun et al confirmed that miR-181a directly targeted TRAIL and alleviated the disarrangement of intervertebral disc tissue in intervertebral disc degeneration mice [7]; miR-133a was demonstrated to significantly promote type II collagen Journal of Healthcare Engineering expression by targeting MMP9 in NP cells [8]
Particular attention has been paid to the expression of miRNAs and their functions in relieving the symptoms of IVDD. e studies conducted in vivo experiments using the IVDD rat model identified that miR-185 and miR-143-5p were connected with NP cell apoptosis in IVDD [25, 26]. miR-98 could reduce apoptosis in many diseases, such as sepsis and acute myocardial infarction [27, 28]
Summary
Cervical intervertebral disc degeneration (IVDD) is a common clinical disease, and it affects more than 62% of patients whose age was over 40 years, with or without any clinical symptom [1]. More and more studies indicated that the excessive apoptosis of nucleus pulposus (NP) cells had a vital influence on the progress of IVDD [5]. Accumulating evidence indicates that the levels of miRNAs are frequently dysregulated in intervertebral disc degeneration, which can induce NP cell apoptosis and destroy the balance of cellmatrix synthesis and degradation [7,8,9], for instance, Sun et al confirmed that miR-181a directly targeted TRAIL and alleviated the disarrangement of intervertebral disc tissue in intervertebral disc degeneration mice [7]; miR-133a was demonstrated to significantly promote type II collagen
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