Maresin1 alleviates inflammation and improves extracellular matrix regeneration after intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is characterized by excessive inflammation and extracellular matrix (ECM) degradation in the nucleus pulposus (NP), with limited current therapeutic options. Specialized pro-resolving mediators (SPMs) such as Maresin 1 (MaR1) have emerged as key regulators of inflammation resolution and tissue repair. Here, we report that MaR1 and its receptor LGR6 are significantly downregulated in degenerated human NP tissues, suggesting a loss of endogenous resolution capacity. Exogenous MaR1 administration effectively attenuated IL-1β-induced inflammation and ECM degradation in human NP cells and alleviated IVDD progression in rat models. Mechanistically, MaR1 simultaneously suppressed the catabolic AP-1/MMP pathway and activated the pro-anabolic OSR1/GDF7 axis, rebalancing ECM homeostasis. Notably, the therapeutic efficacy of MaR1 was completely abrogated in Lgr6-knockout mice, demonstrating that LGR6 is the indispensable mediator of MaR1's protective effects in vivo. Our findings identify the MaR1-LGR6 axis as a critical regulator of disc homeostasis and highlight MaR1 supplementation as a novel and promising strategy for IVDD treatment.