Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice

Abstract

Purpose Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complexTramtrack-Bric-a-brac and cap'n'collar homology 1 deficient (Bach 1-/-) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress. Methods Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9-C10 caudal discs in 12-week-old Bach 1-/-and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1-/-and wild-type mice. Results In the age-related model, there were no significant differences between Bach 1-/-and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1-/-mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1-/-mice. Conclusions Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.

The unfolded protein response mediated by PERK is casually related to the pathogenesis of intervertebral disc degeneration

“…is what initially triggers ER stress in the AF cells, and that the ensuing UPR serves to initiate a vicious cycle of IVD degeneration through inducing catabolic factors and thereby further damaging the IVD matrix. Although more studies are required to address this hypothesis, this may also explain why IVD degeneration is an irreversible and progressive event in humans and why a single puncture to the IVDs promotes IVD degradation in rodents …”

ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

“…Notably, the expression of HO-1 in the punctured discs of Bach 1−/− mice was significantly higher than that in the punctured discs of wild-type mice. Concomitantly, the progression of IDD in Bach 1−/− mice was slower than that in wild-type mice [96]. AGEs were found to accumulate in the discs of diabetic mice or rats that manifest accelerated degenerative changes.…”

Histological and reference system for the analysis of mouse intervertebral disc

“…An early study that collated and analyzed almost 200 human IVD histological specimens to characterize key changes with aging, compiled a detailed grading system . Similar histological/morphological IVD changes have been assessed in animal models including the rabbit, goat, rat, mice, dog, and sheep, with scoring systems based on other previous human and animal studies, or a combination of different models . This has resulted in a multitude of histological assessments of the IVD.…”

“…In studies of mouse IVD, scoring systems have utilized structural changes of the NP/AF/EP, abnormalities in extracellular matrix, histological staining patterns, presence of clefts/fissures, and cellularity . Some studies solely describe morphological observations of cells and tissues, while others have a point‐based scoring system to assess various IVD regions, which are summed to give an overall IVD quality score .…”