To identify regulatory ncRNA molecules that can cause differential expression of CDH2 in intervertebral disc degeneration (IDD) and explore whether there are other ways to affect the progression of IDD. A primary culture of human nucleus pulposus (NP) cells was established and identified by immunofluorescence. An in vitro IDD model was constructed by compressing human NP cells, and the MTT assay was used to measure cell viability. Changes in the ncRNA group were analysed by RNA-seq. The expression levels of hsa_circ_7042, CDH2, and miR-369-3p were detected by qPCR. Cell apoptosis, senescence, and extracellular matrix (ECM) metabolism were detected by flow cytometry, β-galactosidase staining, and Western blotting. hsa_circ_7042, miR-369-3p, and bone morphogenetic protein 2 (BMP2) were verified by luciferase and RNA immunoprecipitation (RIP) analyses. The PI3K/Akt pathway was validated by transfection of BMP2 siRNA. Furthermore, a mouse model of lumbar spine instability was constructed. circ_7042 adenovirus was packaged and injected into the intervertebral discs of mice, and the influence of circ_7042 overexpression on intervertebral disc degeneration was determined. Western blotting, qPCR, and flow cytometry analyses confirmed that overexpression of circ_7042 could downregulate miR-369-3p and upregulate the expression of CDH2 and BMP2 in IDD cell and animal models. Additionally, the levels of apoptotic and senescent cells decreased, and ECM degradation decreased. The PI3K/Akt pathway was significantly activated after circ_7042 was overexpressed. The injection of circ_7042-overexpressing adenovirus effectively reduced ECM degradation and the level of apoptosis in NP tissue. circ_7042 could upregulate the expression of CDH2 and BMP2 by absorbing miR-369-3p, and the increased BMP2 activated the PI3K/Akt pathway, thus improving IDD.

中文翻译：

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Circ0007042 通过吸附 miR-369 上调 BMP2 并激活 PI3K/AKt 通路来缓解椎间盘退变

鉴定可导致椎间盘退变（IDD）中CDH2差异表达的调节性ncRNA分子，并探讨是否有其他方式影响IDD的进展。建立人髓核 (NP) 细胞的原代培养物并通过免疫荧光鉴定。通过压缩人NP细胞构建体外IDD模型，并使用MTT法测量细胞活力。通过 RNA-seq 分析 ncRNA 组的变化。qPCR检测hsa_circ_7042、CDH2和miR-369-3p的表达水平。通过流式细胞术、β-半乳糖苷酶染色和蛋白质印迹检测细胞凋亡、衰老和细胞外基质 (ECM) 代谢。hsa_circ_7042，miR-369-3p，和骨形态发生蛋白 2 (BMP2) 通过荧光素酶和 RNA 免疫沉淀 (RIP) 分析进行了验证。通过转染 BMP2 siRNA 验证了 PI3K/Akt 通路。此外，还构建了腰椎不稳的小鼠模型。将circ_7042腺病毒包装后注射到小鼠椎间盘中，测定circ_7042过表达对椎间盘退变的影响。蛋白质印迹、qPCR 和流式细胞术分析证实，circ_7042 的过表达可以下调 miR-369-3p 并上调 IDD 细胞和动物模型中 CDH2 和 BMP2 的表达。此外，凋亡和衰老细胞的水平降低，ECM 降解减少。circ_7042过表达后，PI3K/Akt通路被显着激活。注射 circ_7042 过表达腺病毒有效降低了 ECM 降解和 NP 组织中的细胞凋亡水平。circ_7042可以通过吸收miR-369-3p上调CDH2和BMP2的表达，增加的BMP2激活PI3K/Akt通路，从而改善IDD。