Experimental study of lumbar ligamentum flavum hypertrophy induced in bipedal mice

Lumbar spinal stenosis (LSS) is a common degenerative disease among the elderly. The role that mechanical stress-induced hypertrophic ligamentum flavum (HLF) plays in patients with LSS remains unclear. Here, we used a finite element analysis to investigate the stress characteristics on the ligamentum flavum (LF) and evaluate the feasibility of a mouse model of HLF. First, we induced a bipedal posture in mice by taking advantage of their hydrophobia. A micro-CT scan was performed to examine their spinal change during bipedal posture. A finite element analysis showed that the stress and strain on the upright posture were significantly increased compared with those on the sprawling posture. Tissue staining showed that the degeneration degree of the LF in bipedal standing group gradually increased over the modeling period. The amount of elastic fibers decreased under HLF, whereas the amount of collagen fibers, the number of the LF cells, and the expression of fibrosis-related factors increased. Compared with aged group, LF degeneration was more severe in the bipedal standing group. Our findings demonstrate that the increased stress caused by a posture change causes HLF and that a bipedal mouse model can be used to study HLF in vivo.