Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Cell Biochem. 2018 Sep;119(9):7218-7225. doi: 10.1002/jcb.26888. Epub 2018 May 15.
Growing evidences suggested that microRNAs (miRNAs) played important roles in the development of intervertebral disc degeneration (IDD). However, the expression level and function of miR-665 in IDD remain unknown. In this study, we showed that the expression level of miR-665 was upregulated in degenerative human NP samples. In addition, miR-665 expression level gradually increased with the exacerbation of disc degeneration grade. Moreover, miR-665 expression level was positively associated with the Pfirrmann grade. Ectopic expression of miR-665 promoted NP cell growth. Furthermore, miR-665 overexpression decreased aggrecan and Col II expression and ectopic expression of miR-665 increased MMP-3 and MMP-13 expression in NP cell. We identified growth differentiation factor 5 (GDF5) was a direct target gene of miR-665 in NP cell and enforced expression of miR-665 decreased GDF5 expression. Elevated expression of miR-665 enhanced NP cell proliferation and decreased aggrecan and Col II expression. In addition, ectopic expression of miR-665 increased MMP-3 and MMP-13 expression through inhibiting GDF5 expression in NP cells. These results suggested that dysregulated miR-665 expression might act an important role in the development of IDD.
越来越多的证据表明 microRNAs（miRNAs）在椎间盘退行性变（IDD）的发展中起重要作用。然而，miR-665 在 IDD 中的表达水平和功能仍不清楚。在本研究中，我们表明 miR-665 的表达水平在退变的人 NP 样本中上调。此外，miR-665 的表达水平随着椎间盘退变程度的加重而逐渐升高。此外，miR-665 的表达水平与 Pfirrmann 分级呈正相关。miR-665 的异位表达促进 NP 细胞生长。此外，miR-665 过表达降低了聚集蛋白聚糖和 Col II 的表达，而 miR-665 的异位表达增加了 NP 细胞中 MMP-3 和 MMP-13 的表达。我们确定生长分化因子 5（GDF5）是 NP 细胞中 miR-665 的直接靶基因，强制表达 miR-665 降低了 GDF5 的表达。miR-665 表达水平的升高增强了 NP 细胞的增殖，降低了聚集蛋白聚糖和 Col II 的表达。此外，miR-665 的异位表达通过抑制 NP 细胞中 GDF5 的表达，增加了 MMP-3 和 MMP-13 的表达。这些结果表明，miR-665 表达的失调可能在 IDD 的发展中起重要作用。
