The increased motion of lumbar induces ligamentum flavum hypertrophy in a rat model

Abstract

Background The purpose of this study was to establish a novel rat model for ligamentum flavum (LF) hypertrophy using increased motion of lumbar and to elucidate the etiology of (LFH). Methods A total number of 30 male rats were used. The increased motion of lumbar was induced by surgical resection of L5/6 posterior elements (n = 15). The other rats underwent a sham operation (n = 15). After 8 weeks, all rats were taken lateral plain X-rays. The LF from L5/6 in both groups were harvested to investigate histological, immunohistological, and real-time PCR analysis. Results According to radiological results, the disc height ratio, flexion ratio, and extension ratio were larger in the rats in the experimental group than that of in the sham group. The HE staining showed that the LF thickness in the experimental group significantly increased in comparison to the sham group. The Masson trichrome staining showed that the ratio of elastic fibers to collagen fibers in experimental group was lower than that in the sham group. The protein and gene expression of TGF-β1, TNF-α, IL-1β, and Col 1 were significantly higher in the experimental group than that in the sham group. Conclusion A relatively safe, simple, and rapid rat model of LFH using increased motion of lumbar was established. The increased motion of lumbar could lead to high expression of inflammatory and fibrotic factors in LF, causing the accumulation of collagen fibers and decreasing of elastic fibers.

Histological difference in ligament flavum between degenerative lumbar canal stenosis and non-stenotic group: A prospective, comparative study

“…Sairyo et al [ 1 ] had proposed that LFH occurs due to degenerative changes with aging process, and also due to increased mechanical stress occurring in instability. Wang et al [ 14 ] have experimentally demonstrated increased motion in lumbar spine induced LFH. Chuang et al [ 15 ] have found that age-related LFH occurred due to activation of the Akt and MAPK (apoptotic) pathways.…”

An in vivo model of ligamentum flavum hypertrophy from early‐stage inflammation to fibrosis

“…However, limitations in the mouse exist due to anatomical differences between human and mouse LF footprint within the spinal canal 25 . Alternatively, larger rodent models, such as the rat, more closely represent the human LF in terms of histological features, anatomical position, and tissue composition, and may be more useful for evaluating therapeutic interventions 27,28 . In the rat, Sato et al found that posterior destabilization of lumbar spine intended to increase flexion and thus cause overloading on the LF, caused enlargement of the dorsal surface layer of the LF.…”

“…However, changes to the mid‐substance of the LF ECM was not investigated. Recent studies by Wang et al , tested the effect of increased lumbar segment motion by resection of spinous process, grinding of facet joints and removal of paraspinal muscle 27‐29 . This approach resulted in LF hypertrophy, with increased LF thickness and area, increased area of matrix containing collagen fibers, but no change in area containing elastic fibers, suggesting that this model simulated mild LF hypertrophic changes.…”

Macrophage migration inhibitory factor takes part in the lumbar ligamentum flavum hypertrophy

“…Recently, the major pathological elements of LF hypertrophy have been proved to be mechanical and metabolic ( 3 , 4 ). Pathologically, the hypertrophy of LF is associated with scar repair secondary to mechanically induced micro-injury and metabolic accumulation mediated biochemical reaction, among which the inflammatory reaction is important ( 5 , 6 ).…”