High-glucose environment accelerates annulus fibrosus cell apoptosis by regulating endoplasmic reticulum stress.

Lianglong Pang,Keshi Yang,Zhi Zhang

doi:10.1042/bsr20200262

Abstract

Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. However, how DM affects annulus fibrosus (AF) biology remains unclear. The present study was aimed to investigate the effects and mechanism of high glucose on AF cell biology. Rat AF cells were cultured in baseline medium and culture medium with 0.2 M glucose. The inhibitor 4-PBA was added along with the high glucose culture medium to study the role of endoplasmic reticulum (ER) stress in this process. Compared with the control cells, high glucose significantly increased cell apoptosis ratio and caspase-3/9 activity, up-regulated mRNA/protein expression of Bax and caspase-3/cleaved caspase-3, but down-regulated mRNA/protein expression of Bcl-2. Moreover, high glucose increased mRNA and protein expression of CHOP, ATF-6 and GRP78. However, once ER stress was inhibited by the inhibitor 4-PBA in the high glucose group, cell apoptosis ratio and caspase-3/9 activity were decreased, mRNA/protein expression of Bax and caspase-3/cleaved caspase-3 was down-regulated, but mRNA/protein expression of Bcl-2 was up-regulated. In conclusion, high glucose condition can promote AF cell apoptosis through inducing ER stress. The present study helps us understand the mechanism of disc degeneration in DM patients.

Highlights

Intervertebral disc degeneration is the main cause of approximately 40% of low back pain in adults worldwide, which seriously affects social health care system [1]
The results showed that high glucose significantly increased their activity compared with the control group, whereas addition of 4-PBA decreased both caspase-3 activity and caspase-9 activity in the high glucose group (Figure 2)
Our results showed that high glucose culture significantly increased cell apoptosis ratio and caspase-3/9 activity, up-regulated mRNA/protein expression of Bax, caspase-3/cleaved caspase-3, whereas down-regulated mRNA /protein expression of Bcl-2, indicating that this designed concentration of high glucose promotes disc Annulus fibrosus (AF) cell apoptosis in the present study

Summary

Introduction

Intervertebral disc degeneration is the main cause of approximately 40% of low back pain in adults worldwide, which seriously affects social health care system [1]. More studies about the relationship between the etiology and disc cell apoptosis are essential to retard disc degeneration. Several studies have reported that DM is a potential etiological factor of intervertebral disc degeneration [10,11,12,13,14,15]. Some researchers have demonstrated that high glucose can promote apoptosis of disc cartilage endplate cells and notochordal cells, and accelerate the progression of disc degeneration [16,17]. Previous studies have shown that high glucose induces apoptosis or premature senescence of AF cells [19,20]. The mechanism behind the effects of high glucose on AF cell apoptosis remains unclear

Methods

Results

Conclusion