Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance

Abstract

The intervertebral disc is the largest avascular low-nutrient organ in the body. Thus, resident cells may utilize autophagy, a stress-response survival mechanism, by self-digesting and recycling damaged components. Our objective was to elucidate the involvement of autophagy in rat experimental disc degeneration. In vitro, the comparison between human and rat disc nucleus pulposus (NP) and annulus fibrosus (AF) cells found increased autophagic flux under serum deprivation rather in humans than in rats and in NP cells than in AF cells of rats (n = 6). In vivo, time-course Western blotting showed more distinct basal autophagy in rat tail disc NP tissues than in AF tissues; however, both decreased under sustained static compression (n = 24). Then, immunohistochemistry displayed abundant autophagy-related protein expression in large vacuolated disc NP notochordal cells of sham rats. Under temporary static compression (n = 18), multi-color immunofluorescence further identified rapidly decreased brachyury-positive notochordal cells with robust expression of autophagic microtubule-associated protein 1 light chain 3 (LC3) and transiently increased brachyury-negative non-notochordal cells with weaker LC3 expression. Notably, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic death was predominant in brachyury-negative non-notochordal cells. Based on the observed notochordal cell autophagy impairment and non-notochordal cell apoptosis induction under unphysiological mechanical loading, further investigation is warranted to clarify possible autophagy-induced protection against notochordal cell disappearance, the earliest sign of disc degeneration, through limiting apoptosis.

Concepts of Regeneration for Spinal Diseases in 2021

“…Yurube T et al [3] observed in vivo autophagy impairment in NP notochordal cells and apoptosis induction in NP non-notochordal cells under unphysiological mechanical loading-induced experimental disc degeneration of rat tails, supporting the interpretation that autophagy could protect notochordal cell homeostasis through limiting apoptosis in the disc NP.…”

O-GlcNAc transferase regulates intervertebral disc degeneration by targeting FAM134B-mediated ER-phagy

“…In addition, in an AT-1 transgenic mouse model of progeria, increased transport of cytosolic acetyl‐CoA into the ER lumen and blockade of ER autophagic recycling were found to be closely linked to defective ER-phagy, and functional restoration of ER-phagy rescued the aging phenotype in total and extended the lifespan 48 . Furthermore, it has been established that autophagy is crucial for the maintenance of IVD homeostasis and that autophagy impairment is directly involved in the induction of irregular notochordal cell disappearance, nonnotochordal cell apoptosis and senescence 49 – 51 . Therefore, we investigated the effects of FAM134B-mediated ER-phagy on cell functionality and survival in human NP cells under nutrient starvation conditions and found that FAM134B-mediated ER-phagy was activated in response to ND and that FAM134B knockdown significantly aggravated ND-induced apoptosis and senescence.…”

Comparison Two Methods between Injection Saline and External Fixator in Rat Tail Disc Degeneration

“…Intervertebral disc degeneration (IVDD) is a key recognizable fact for back and neck pain in adults leading to decrease quality life sometimes making disable (1)(2)(3)(4). IVDD is a pathological and physiological process that can be chronic and progressive (1).The disease is of widespread prevalence .…”

“…About 80% of the mature individuals would be subjected to back and neck pain at any stages in their life (2,5,6). Intervertebral disc (IVD),an important element which can tolerate various kinds of load depending on the intensity of load (7).Many studies have been conducted, where mentioned excessive external stress, hereditary disease, obesity and aging are most common enhancer of IVDD (1,3,6,8). However, mechanical stimulus is another important key contributor for IVDD, when it exceeds tolerable margin of load baring elements (9).…”

“…Reasonable mechanical signal creates defensive effect on IVD but, too much mechanical pressure often exacerbates IVD cells diminish. IVD is composed of three distinct but interdependent tissues: central gelatinous nucleus pulposus (NP), outer annulus fibrosus (AF) and cartilage end plates on the superior and inferior surfaces (1,3,10). NP cells play a vital role to maintain normal skeleton and physiological function of IVD by producing extracellular matrix (ECM), including type II collagen and proteoglycans (mainly aggrecans) (1,10).Innermost NP cells are the basic part of IVD.…”