Tbxt alleviates senescence and apoptosis of nucleus pulposus cells through Atg7-mediated autophagy activation during intervertebral disk degeneration.

Intervertebral disk degeneration (IDD) is a significant cause of low back pain, characterized by excessive senescence and apoptosis of nucleus pulposus cells (NPCs). However, the precise mechanisms behind this senescence and apoptosis remain unclear. This study aimed to investigate the role of T-box transcription factor T () in IDD both in vitro and in vivo, using a hydrogen peroxide (HO)-induced NPCs senescence and apoptosis model, as well as a rat acupuncture IDD model. First, the expression of p16 and cleaved-caspase 3 significantly increased in degenerated human NPCs, accompanied by a decrease in Tbxt expression. Knockdown of exacerbated senescence and apoptosis in the HO-induced NPCs degeneration model. Conversely, upregulation of alleviated these effects induced by HO. Mechanistically, bioinformatic analysis revealed that the direct downstream target genes of were highly enriched in autophagy-related pathways, and overexpression of significantly activated autophagy in NPCs. Moreover, the administration of the autophagy inhibitor, 3-methyladenine, impeded the impact of on the processes of senescence and apoptosis in NPCs. Further investigation revealed that enhances autophagy by facilitating the transcription of through its interaction with a specific motif within the promoter region. In conclusion, this study suggests that mitigates HO-induced senescence and apoptosis of NPCs by activating ATG7-mediated autophagy. This study investigates the role of in IDD. The results demonstrate that knockdown of exacerbates HO-induced senescence and apoptosis in NPCs and IDD, whereas upregulation of significantly protects against IDD both in vivo and in vitro. Mechanistically, in the nucleus, enhances the transcription of ATG7, leading to increased expression of ATG7 protein levels. This, in turn, promotes elevated autophagy levels, ultimately alleviating IDD.