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 LF associated with the sprawling and bipedal postures were concentrated at the facet joint level. Moreover, 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 facet joint and the LF thickness of the 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. In addition, no difference was found in facet joint degeneration between the 10-week modeling mice and the aged mice; however, LF degeneration was more severe in the former 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.