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Asian Spine J. 2015 Apr;9(2):155-61. doi: 10.4184/asj.2015.9.2.155. Epub 2015 Apr 15.

Effect of high glucose on stress-induced senescence of nucleus pulposus cells of adult rats.

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1
Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, The Catholic University of Korea College of Medicine, Uijeongbu, Korea.

Abstract

STUDY DESIGN:

In vitro cell culture model.

PURPOSE:

We investigated the effect of diabetes mellitus (DM) on senescence of adult nucleus pulposus (NP) cells.

OVERVIEW OF LITERATURE:

DM is a major public health issue worldwide, especially adult-onset (type 2) DM. DM is also thought to be an important etiological factor in disc degeneration. Hyperglycemia is considered to be a major causative factor in the development of DM-associated diseases through senescence. However, little is known about the effects of DM on senescence in adult NP cells.

METHODS:

Adult NP cells were isolated from 24-week-old rats, cultured, and placed in either 10% fetal bovine serum (FBS, normal control) and 10% FBS plus two different high glucose concentrations (0.1 M or 0.2 M; experimental conditions) for 1 or 3 days. We identified and quantified the occurrence of senescence in adult rat NP cells using senescence-associated-beta-galactosidase (SA-β-Gal) staining. We also investigated the expression of proteins related to the replicative senescence (p53-p21-pRB) and stress-induced premature senescence (p16-pRB) pathways.

RESULTS:

The mean SA-β-Gal-positive percentage was increased in adult rat NP cells treated with high glucose in a dose- and time-dependent manner. Both high glucose levels increased the expression of p16 and pRB proteins in adult rat NP cells. However, the levels of p53 and p21 proteins were decreased in adult rat NP cells treated with both high glucose concentrations.

CONCLUSIONS:

The current study demonstrated that high glucose accelerated stress-induced senescence in adult rat NP cells in a dose- and time-dependent manner. Accelerated stress-induced senescence in adult NP cells could be an emerging risk factor for intervertebral disc degeneration in older patients with DM. These results suggest that strict blood glucose control is important in prevent or delaying intervertebral disc degeneration in older patients with DM.

KEYWORDS:

Adult nucleus pulposus cells; High glucose; Intervertebral disc degeneration; Senescence

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