The Effect of Mechanical Stress on Ligamentum Flavum Hypertrophy; Utilization of Novel In Vitro Multi-torsional Stretch Loading Device

Objective: We developed a novel multi-torsional mechanical stretch stress (MSS) loading device for ligamentum flavum (LF) cells and evaluated its influence on the development of ligamentum flavum hypertrophy (LFH), a common cause of lumbar spinal canal stenosis. Materials: and Methods Stretch strength of the device was optimized by applying 5% and 15% MSS loads for 24, 48, and 72 h. A cytotoxicity assay of human LF cells was performed and the results were compared to control (0%) MSS. Inflammatory markers (interleukin [IL]-6, IL-8), vascular endothelial growth factor [VEGF], and extracellular matrix (ECM)-regulating cytokines (matrix metalloproteinase [MMP]-1, MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase [TIMP]-1 and TIMP-2) were quantified via enzyme-linked immunosorbent assay. Results: Using our multi-torsional MSS loading device, 5% MSS for 24 h was optimal for LF cells. Under this condition, the IL-6 and IL-8 levels, VEGF level, and MMR-1, MMR-3, and TIMP-2 were significantly increased, compared to the control. Conclusion: Using the novel multi-torsional MSS loading device we confirmed that, mechanical stress enhances the production of inflammatory cytokines and angiogenic factors, and altered the expression of ECM-regulating enzymes, possibly triggering LFH. This discovery enhances our understating of the effects of mechanical stress on LFH.