Swimming ameliorates intervertebral disc degeneration accompanied by Rpl23a downregulation and changes in its immune-inflammatory pathway.

BACKGROUND

Intervertebral disc degeneration (IVDD) is characterized by persistent inflammation and extracellular matrix degradation, but the driving mechanism of immune dysregulation in the intervertebral disc remains unclear. Ribosomal protein L23a (Rpl23a) participates in various inflammatory diseases, but its role in the intervertebral disc immune microenvironment has not been studied. This study investigated the mechanism of Rpl23a in regulating immune interactions in IVDD and evaluated whether exercise intervention can interfere with this signaling axis.

METHODS

Bulk and single-cell RNA sequencing datasets (GSE189551, GSE153066) were analyzed to identify differentially expressed genes in IVDD and determine their cellular origins. Ligand-receptor interaction analysis was used to predict the immune cell communication network. In vitro experiments explored the role of Rpl23a in immune activation and NF-κB pathway activity. A rat IVDD model was established in vivo to evaluate the effect of swimming on Rpl23a-mediated inflammatory responses.

RESULTS

Rpl23a was significantly upregulated in degenerated intervertebral discs, mainly expressed in fibroblasts. Intercellular communication analysis revealed extensive crosstalk between Rpl23a-positive fibroblasts, macrophages, and T lymphocytes, contributing to the formation of a pro-inflammatory microenvironment. In vitro experiments showed that Rpl23a overexpression increased the secretion of TNF-α and IL-1β, activated NF-κB signaling, and further induced cell apoptosis and matrix catabolism; Rpl23a knockdown reversed these effects. Swimming alleviated IVDD in rats, accompanied by reduced Rpl23a expression, decreased immune cell infiltration, and inhibited NF-κB activation.

CONCLUSION

Rpl23a is closely related to NF-κB signaling activation and may participate in the formation of a pathological immune microenvironment. Swimming can alleviate IVDD, accompanied by Rpl23a downregulation and NF-κB pathway inhibition, suggesting that Rpl23a may mediate the intervertebral disc protective effects of exercise and provide a theoretical reference for exercise therapy of IVDD.