Abstract
Inflammation plays a key role in intervertebral disc degeneration (IDD). The association between inflammation and endoplasmic reticulum (ER) stress has been observed in many diseases. However, whether ER stress plays an important role in IDD remains unclear. Therefore, this study is aimed at investigating the expression of ER stress in IDD and at exploring the underlying mechanisms of IDD, ER stress, and inflammation. The expression of ER stress was activated in nucleus pulposus cells from patients who had IDD (D-NPCs) compared with patients without IDD (N-NPCs); and both the proliferation and synthesis capacity were decreased by inducer tunicamycin (Tm) and proinflammatory cytokines. Pretreatment of NPCs with 4-phenyl butyric acid (4-PBA) prevented the inflammatory cytokine-induced upregulation of unfolded protein response- (UPR-) related proteins and recovered cell synthetic ability. Furthermore, proinflammatory cytokine treatment significantly upregulated the expression of inositol-requiring protein 1 (IRE1-α) and protein kinase RNA-like ER kinase (PERK), but not activating transcription factor 6 (ATF6). Finally, knockdown of IRE1-α and PERK also restored the biological activity of NPCs. Our findings identified that IRE1-α and PERK might be the potential targets for IDD treatment, which may help illustrate the underlying mechanism of ER stress in IDD.
Highlights
Low back pain (LBP) is a common disease, which may result in patients’ disability and cause great economic burden to society [1]
Our results showed that more dilated and abundant endoplasmic reticulum (ER) were observed in D-nucleus pulposus cells (NPCs) (Figure 1(a))
The results of PCR indicated that the expression of unfolded protein response (UPR) target genes was increased in degenerated NPCs (D-NPCs) compared to nondegenerated NPCs (N-NPCs)
Summary
Low back pain (LBP) is a common disease, which may result in patients’ disability and cause great economic burden to society [1]. Intervertebral disc degeneration (IDD) has been verified as a key factor for LBP [2]. Intervertebral disc (IVD) maintains homeostasis in physiological condition and degeneration can be triggered by several risk factors, such as abnormal mechanical stress, nutrient deficient, and aberrant inflammatory condition [3]. Inflammation is considered an important contribution to IDD [4]. Inflammatory cytokines are significantly associated with the progression of IDD [5,6,7]. Nucleus pulposus cells (NPCs) play an important role in maintaining nucleus pulposus (NP) tissue homeostasis, thereby facilitating the maintenance of spine biomechanics [8]
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