We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Targeting the IL-1β/IL-1Ra pathways for the aggregation of human islet amyloid polypeptide in an ex vivo organ culture system of the intervertebral disc.
- Authors
Wu, Xinghuo; Liao, Zhiwei; Wang, Kun; Hua, Wenbin; Liu, Xianzhe; Song, Yu; Zhang, Yukun; Yang, Shuhua; Yang, Cao
- 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. Back pain: Proteins under pressure Intervertebral disc degeneration (IDD), is caused in part by a protein, hIAPP, that is secreted by the cells that make insulin, a blood sugar regulator. In IDD, the nucleus pulposus in disc degenerate, causing low back pain. Recent research linked formation of hIAPP aggregates with death of intervertebral disc cells. Given inflammation's known role in IDD, Cao Yang at the Huazhong University of Science and Technology, Wuhan, China, and colleagues investigated how hIAPP and inflammation interact in IDD. Using a method they developed to model IDD by applying compression to cultured rat intervertebral disc cells, they showed that accumulation of hIAPP aggregates triggered inflammation and accelerated cell death. Blocking the inflammation decreased hIAPP aggregation and slowed IDD progression. Methods to disrupt hIAPP aggregation hold promise for treatment of IDD.
- Publication
Experimental & Molecular Medicine EMM, 2019, Vol 51, Issue 9, pN.PAG
- ISSN
1226-3613
- Publication type
Article
- DOI
10.1038/s12276-019-0310-7