Abstract Background Lumbar degenerative disc disease (LDD) is a disabling condition which was associated with progressive degeneration of the intervertebral discs. The miR-766-3p and its modulation of SIRT6 remains unclear in LDD. Purpose This study aims to explored the regulated function of miR-766-3p and SIRT6 during LDD. Methods Human nucleus pulposus cells (HNPCs) were treated with lipopolysaccharide (LPS) to construct a model of LDD to simulate inflammatory conditions. RT-qPCR and ELISA assays were employed to measure the expression of miR-766-3p and SIRT6. Additionally, we evaluated the levels of TNF‑α, IL‑1β, IL‑6, aggrecan, and collagen II by ELISA. Dual-luciferase reporter assays validated direct targeting between miR-766-3p and SIRT6. Results We observed that miR-766-3p was upregulated in LDD patients, and SIRT6 was downregulated. It is consistent with the changes in LPS-induced HNPCs. Additionally, when we inhibited the miR-766-3p and overexpressed SIRT6, inflammatory cytokines decreased, whereas aggrecan and collagen II increased. Moreover, the inhibition of miR-766-3p increased SIRT6, which was decreased by LPS. And the binding relationship between miR-766-3p and SIRT6 was confirmed by luciferase activity. MiR-766-3p mimic reversed the effects of elevated SIRT6 expression. Conclusion The findings identify the miR-766-p/SIRT6 axis as a critical regulator mediating inflammatory responses and driving extracellular matrix degradation during LDD. Targeting this molecular pathway would offer novel therapeutic strategies for mitigating tissue damage of LDD.
An et al. (Wed,) studied this question.