Abstract
Intervertebral disc degeneration (IDD) is characterized by excessive apoptosis of nucleus pulposus (NP) cells and hyperactive extracellular matrix (ECM) catabolism. Our previous studies revealed the relationship between human islet amyloid polypeptide (hIAPP) and NP cell apoptosis. However, the role of hIAPP aggregates in IDD has not yet been investigated. This study aimed to determine whether the accumulation of hIAPP aggregates promotes IDD progression. The aggregation of hIAPP increased in human NP tissues during IDD. The deposition of hIAPP aggravated the compression-induced IDD that promoted NP cell apoptosis and ECM degradation via IL-1β/IL-1Ra signaling in an ex vivo rat disc model. Moreover, neutralizing IL-1β augmented the protective effects of hIAPP overexpression by decreasing hIAPP aggregation in human NP cells. These results suggest that the aggregation of hIAPP promotes NP cell apoptosis and ECM degradation ex vivo and in vitro by disrupting the balance of IL-1β/IL-1Ra signaling.
Highlights
Low back pain (LBP) associated with intervertebral disc degeneration (IDD) is a common cause of disability worldwide; ~80% of people will suffer from LBP at some point in their lives[1]
Costaining with Thioflavin S (Th-S) clearly showed that the expression of collagen II decreased as human islet amyloid polypeptide (hIAPP) aggregated in degenerative disc tissues (Fig. 1b)
Given that IDD is characterized by the depletion of resident cells and an elevation in the apoptosis rate, the expression of caspase-3 and FAS were detected in IS and IDD tissues (Fig. 1e, f)
Summary
Low back pain (LBP) associated with intervertebral disc degeneration (IDD) is a common cause of disability worldwide; ~80% of people will suffer from LBP at some point in their lives[1]. Many factors, such as obesity, smoking and diabetes mellitus (DM), are thought to be involved in IDD progression[2,3]. The etiology and pathogenesis of IDD remain unknown. IDD is characterized by the depletion of resident cells and the degradation of the extracellular matrix (ECM)[5]. An increase in the apoptosis level of NP cells contributes to excessive cell expression is related to the development of IDD and that
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