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
Tissue Engineering for Orthopaedics & Mechanobiology, Bone & Joint Program, Department for BioMedical Research (DBMR), Faculty of Medicine, University of Bern, 3008, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, 3012, Bern, Switzerland.
Sci Rep. 2025 May 6;15(1):15849. doi: 10.1038/s41598-025-00538-w.
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 α and β.
椎间盘（IVD）退变是年轻成年人下腰痛的主要原因，而软骨终板（CEP）可能在IVD早期退变中起关键作用。为了阐明促炎细胞因子对CEP力学生物学的影响，将人CEP细胞接种到2%的琼脂糖中，动态压缩至7%，并用肿瘤坏死因子（TNF）刺激。据推测，动态压缩足以诱导合成代谢，而TNF刺激则会诱导分解代谢。TNF通过下调合成代谢基因表达以及增加与椎间盘突出、细菌抑制和疼痛相关的促炎蛋白分泌，足以在人CEP细胞中诱导分解代谢的、时间依赖性反应。然而，7%的应变或支架材料琼脂糖可能不会导致整合素的完全激活和促炎途径的下调，部分原因是整合素亚基α和β的基因表达未发生变化。
