| First Author | Burt KG | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 23 | Pages | eadj3194 |
| PubMed ID | 38848366 | Mgi Jnum | J:352742 |
| Mgi Id | MGI:7658340 | Doi | 10.1126/sciadv.adj3194 |
| Citation | Burt KG, et al. (2024) Nuclear factor kappaB overactivation in the intervertebral disc leads to macrophage recruitment and severe disc degeneration. Sci Adv 10(23):eadj3194 |
| abstractText | Persistent inflammation has been associated with severe disc degeneration (DD). This study investigated the effect of prolonged nuclear factor kappaB (NF-kappaB) activation in DD. Using an inducible mouse model, we genetically targeted cells expressing aggrecan, a primary component of the disc extra cellular matrix, for activation of the canonical NF-kappaB pathway. Prolonged NF-kappaB activation led to severe structural degeneration accompanied by increases in gene expression of inflammatory molecules (Il1b, Cox2, Il6, and Nos2), chemokines (Mcp1 and Mif), and catabolic enzymes (Mmp3, Mmp9, and Adamts4). Increased recruitment of proinflammatory (F4/80(+),CD38(+)) and inflammatory resolving (F4/80(+),CD206(+)) macrophages was observed within caudal discs. We found that the secretome of inflamed caudal disc cells increased macrophage migration and inflammatory activation. Lumbar discs did not exhibit phenotypic changes, suggestive of regional spinal differences in response to inflammatory genetic overactivation. Results suggest prolonged NF-kappaB activation can induce severe DD through increases in inflammatory cytokines, chemotactic proteins, catabolic enzymes, and the recruitment and activation of macrophage cell populations. |
