Circular RNA hsa_circ_0083756 promotes intervertebral disc degeneration by sponging miR‐558 and regulating TREM1 expression

Abstract

Objectives Intervertebral disc degeneration (IVDD) is a leading cause of low back pain. Circular RNAs (circRNAs) have been demonstrated to exert vital functions in IVDD. However, the role and mechanism of hsa_circ_0083756 in the development of IVDD remain unclear. Materials and methods RT‐qPCR was performed to detect expressions of hsa_circ_0083756, miR‐558 and TREM1 in nucleus pulposus (NP) tissues and cells. CCK8 assay, flow cytometry, TUNEL assay, RT‐qPCR and WB were used to clarify the roles of hsa_circ_0083756 in NP cells proliferation and extracellular matrix (ECM) formation. Bioinformatics analyses, dual‐luciferase reporter gene experiment, RNA immunoprecipitation (RIP) assay and FISH assay were performed to predict and verify the targeting relationship between hsa_circ_0083756 and miR‐558, as well as that between miR‐558 and TREM1. Ultimately, the effect of hsa_circ_0083756 on IVDD was tested through anterior disc‐puncture IVDD animal model in rats. Results hsa_circ_0083756 was upregulated in degenerative NP tissues and cells. In vitro loss‐of‐function and gain‐of‐function studies suggested that hsa_circ_0083756 knockdown promoted, whereas hsa_circ_0083756 overexpression inhibited NP cells proliferation and ECM formation. Mechanistically, hsa_circ_0083756 acted as a sponge of miR‐558 and subsequently promoted the expression of TREM1. Furthermore, in vivo study indicated that silencing of hsa_circ_0083756 could alleviate IVDD in rats. Conclusions hsa_circ_0083756 promoted IVDD via targeting the miR‐558/TREM1 axis, and hsa_circ_0083756 may serve as a potential therapeutic target for the treatment of IVDD.

Therapeutic factors and biomaterial-based delivery tools for degenerative intervertebral disc repair

“… Cheng et al (2018) found that circVMA21 can adsorb miRNA-200c, reduce the expression of its target X-linked inhibitor of apoptosis protein (XIAP), and successfully alleviate the degenerative changes of NP by injecting circVMA21 into a rat IDD model. Du et al (2022) found that the expression of circ_0083756 exhibited a significant rise in degenerative NP tissues and cells, adsorbing miRNA-558, promoting the process of IVD, and alleviating IDD in a rat model by silencing circ-83756. It should be noted that although some circRNA have different functions in regulating IVDD, the role and underlying mechanisms of circRNA in IVDD are still largely vague and require further research.…”

Circular RNA and intervertebral disc degeneration: unravelling mechanisms and implications

“… 7. Du et al ( Du et al, 2022 ) discovered that hsa_circ_ 0083756 expression is increased in tissues and cells with NP degeneration. In vitro functional studies showed that circ_ 0083756 knockdown promotes NP cell proliferation and ECM synthesis and inhibits the release of inflammatory factors, while gene overexpression had the opposite effect.…”

The pathological mechanisms of circRNAs in mediating intervertebral disc degeneration

“…To date, 25 circRNAs associated with IVDD have been reported, including 12 circRNAs that promote IVDD progression and 13 circRNAs that inhibit IVDD progression. Furthermore, 23 circRNAs are reported to be involved in the regulation of ECM metabolism, including 10 circRNAs which promote ECM catabolism (Circ_0004354 [ 63 ], circ_0040039 [ 63 ], circITCH [ 64 ], Circ_0083756 [ 65 ], Circ-FAM169A [ 66 ], circRNA_0000253 [ 67 ], circRNA TIMP2 [ 68 ], cirC_001653 [ 69 ], circRNA_104670 [ 70 ], and circ_0075062 [ 71 ]) and 12 circRNAs that promote ECM synthesis (circ_0022382 [ 72 ], circSPG21 [ 73 ], circSNHG5 [ 74 ], circPKNOX1 [ 75 ], circGLCE [ 76 ], circRNA VMA21 [ 77 ], Circ-grb10 [ 78 , 79 ], circRNA-CIDN [ 80 ], circERCC2 [ 81 ], circSEMA4B [ 82 ], circ-4099 [ 83 ], and circ-FAM169A [ 84 ]) ( Table 1 and Fig. 2 ).…”

“…In addition, circITCH acts as a sponge for miR-17–5p to derepress SOX4, thus promoting the Wnt/β-catenin signaling axis to accelerate apoptosis of NPCs, growth inhibition, and ECM degradation [ 64 ]. Furthermore, Du et al [ 65 ] showed significantly increased expression of circ_0083756 in degenerative nucleus pulposus tissues, which promoted NPCs apoptosis, growth inhibition, and ECM degradation by targeting the miR-558-TREM1 pathway. Guo et al [ 66 ] revealed that the circ-FAM169A-miR-583/BTRC signaling axis regulates the NF-κB pathway-induced IL-1β and TNF-α production and ECM degradation.…”