TNF induces catabolism in human cartilaginous endplate cells in 3D agarose culture under dynamic compression

Crump, Katherine B.; Kanelis, Exarchos; Segarra-Queralt, Maria; Pascuet Fontanet, Andreu; Bermudez-Lekerika, Paola; Alminnawi, Ahmad; Geris, Liesbet; Alexopoulos, Leonidas G.; Noailly, Jérôme; Gantenbein, Benjamin

doi:http://dx.doi.org/10.1038/s41598-025-00538-w

TNF induces catabolism in human cartilaginous endplate cells in 3D agarose culture under dynamic compression

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Crump KB, Kanelis E, Segarra-Queralt M, Pascuet-Fontanet A, Bermudez-Lekerika P, Alminnawi A, et al. TNF induces catabolism in human cartilaginous endplate cells in 3D agarose culture under dynamic compression. Sci Rep. 2025;15(1):15849. DOI: 10.1038/s41598-025-00538-w

Abstract

Intervertebral disc (IVD) degeneration is the leading cause of low back pain in young adults, and the cartilaginous endplate (CEP) is likely to play a key role in early IVD degeneration. To elucidate the effects of pro-inflammatory cytokines on the mechanobiology of the CEP, human CEP cells were seeded into 2% agarose, dynamically compressed up to 7%, and stimulated with tumor necrosis factor (TNF). It was hypothesized that dynamic compression would be sufficient to induce anabolism, while stimulation with TNF would induce catabolism. TNF was sufficient to induce a catabolic, time-dependent response in human CEP cells through downregulation of anabolic gene expression and increased secretion of pro-inflammatory proteins associated with herniated discs, bacteria inhibition, and pain. However, 7% strain or scaffold material, agarose, may not lead to full activation of integrins and downregulation of pro-inflammatory pathways, demonstrated in part through the unchanged gene expression of integrin subunits α5 and β1.