High Glucose Accelerates Autophagy in Adult Rat Intervertebral Disc Cells

Abstract

Study DesignIn vitro cell culture.PurposeThe purpose of this study was to investigate the effect of high glucose on autophagy in adult rat intervertebral disc cells.Overview of LiteratureDiabetes mellitus is considered to be an important etiologic factor for intervertebral disc degeneration, resulting in degenerative disc diseases. A glucose-mediated increase of autophagy is a major causative factor for the development of diseases associated with diabetes mellitus. However, no information is available for the effect of high glucose on autophagy in adult intervertebral disc cells.MethodsNucleus pulposus and annulus fibrosus cells were isolated from 24-week-old adult rats, cultured and placed in either 10% fetal bovine serum (normal control) or 10% fetal bovine serum plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days, respectively. The expressions of autophagy markers, such as beclin-1, light chain 3-I (LC3-I) and LC3-II, autophagy-related gene (Atg) 3, 5, 7 and 12, were identified and quantified.ResultsTwo high glucoses significantly increased the expressions of beclin-1, LC3-II, Atg3, 5, 7, and 12 in adult rat nucleus pulposus and annulus fibrosus cells in a dose- and time-dependent manner. The ratio of LC3-II/LC3-I expression was also increased in a dose-respectively time-dependent manner.ConclusionsThe results suggest that autophagy of adult nucleus pulposus and annulus fibrosus cells might be a potential mechanism for the intervertebral disc degeneration in adult patients with diabetes mellitus. Thus, the prevention of autophagy in adult intervertebral disc cells might be considered as a novel therapeutic target to prevent or to delay the intervertebral disc degeneration in adult patients with diabetes mellitus.

Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration

“…Some studies suggest autophagy as a protective mechanism [117,118]. Other reports showed that autophagy promotes the development of IDD [119,120]. The discrepancy may be caused by differences in the cell culture systems and/or species among the studies.…”

Autophagy: A double-edged sword in intervertebral disk degeneration

“…Under normal physiological conditions, a low basal level of autophagy is observed in NP and AF cells isolated from non-degenerative adult rats, revealing the involvement of autophagy in maintenance of normal disc cell integrity and survival [70]. However, autophagy is significantly increased in degenerative rat NP and AF cells [71,72].…”

Autophagy and mTOR signaling during intervertebral disc aging and degeneration

“…Furthermore, the upregulation of Atg gene expression was observed in human discs with the Pfirrmann 53 grades 4 to 5, compared with grades 1 to 3 49 ; however, the confirmation of autophagic flux at either the protein or organelle levels, using LC3-I to LC3-II conversion and p62/SQSTM1 degradation, was not performed in these cells. Disc cellular autophagy has gained increasing interest, including the activation in both disc NP and AF cells in response to a variety of stress conditions, such as nutrient deprivation, [54][55][56][57] oxidative stress, [58][59][60] compression overload, 61 inflammation, 62 hyperlactatemia, 63 hyperosmolarity, 64 and hypoxia. 65 Meanwhile, evidence regarding mTOR signaling in disc cells is still limited.…”