ABSTRACT: Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and the pathogenesis remains unknown. Recently, an autoregulating circadian rhythm was identified in intervertebral discs (IVDs), the abolition of which led to IDD. The genetic disruption of the mouse IVD molecular clock, specifically through the disruption of Bmal1, predisposes mice to IDD. However, the precise role of circadian gene Bmal1 in IDD remain elusive. In this study, RNA-seq was used to determine differentially expressed genes (DEGs) in rat nucleus pulposus cells (NPCs) treated with Bmal1 shRNA or its negative control lentivirus. GO and KEGG pathway analysis were also performed. In general, 6900 DEGs was identified. The anabolic genes, such as col2a1 and acan, showed significantly decreased expression, whereas catabolic genes, such as MMP-3 and MMP-13, showed significantly upregulated expression. GO analysis was performed to annotate the functions of the DEGs. The DEGs were primarily associated with the processes of cell transcription, behaviour, signal transduction, biological regulation, and protein binding. KEGG pathway analysis revealed that Bmal1 was related to multiple signalling pathways, such as p53, Hedgehog, Wnt, PI3K-Akt, mTOR, Hippo and MAPK. This study, for the first time, analyzes the transcriptome of NPCs in response to Bmal1 diminished, indicating that circadian gene Bmal1 is involved in the establishment and progression of IDD through its wide effects on the viability and function of NPCs.
