Deleting β-catenin in mouse intervertebral disc cells, a model of age-related loss of Wnt signaling, cut expression of the monocyte chemoattractant CCL2 by 58%–79% and reduced myeloid cell burden in uninjured discs by 79%, with injury-induced recruitment falling by 48%. Nucleus pulposus-specific deletion blunted activation of immune signaling pathways after injury on RNA sequencing. Disc resident cells, not infiltrating immune cells, appear to set the chemotactic tone that governs inflammation in the aging spine.
Key Points
- β-catenin deletion reduced disc CCL2 expression by 58%–79%.
- Myeloid cell burden in uninjured discs fell 79% on PET/CT.
- Injury-induced myeloid recruitment dropped 48% without Wnt signaling.
Longevity Analysis
Chronic low back pain in later life tracks with persistent low-grade inflammation and immune cell accumulation in disc tissue, and these data place the disc cells themselves at the controls — their Wnt signaling state determines how loudly they call immune cells in. The same signaling loss that quiets chemotaxis also reduces matrix-building activity, so less inflammatory recruitment comes at the cost of weaker repair capacity in load-bearing tissue. Interventions aimed at spinal resilience must therefore distinguish between suppressing an inflammatory signal and restoring the regenerative output of the cells producing it.
Original published by Wiley Aging Cell, by Tori M. Kroon, Jazz Munitz, Anna Ranzenigo, Martin Umali, William Wang, Jonathan J. Huang, Abraham J. P. Teunissen, Nilsson Holguin .