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.
Xinghuo WuZhiwei LiaoKun WangWenbin HuaXianzhe LiuYu SongYukun ZhangShuhua YangCao YangPublished in: Experimental & molecular medicine (2019)
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.
Keyphrases
- endothelial cells
- extracellular matrix
- cell proliferation
- cell cycle arrest
- induced apoptosis
- induced pluripotent stem cells
- rheumatoid arthritis
- pluripotent stem cells
- oxidative stress
- high glucose
- gene expression
- endoplasmic reticulum stress
- systemic lupus erythematosus
- mass spectrometry
- transcription factor
- drug induced
- diabetic rats
- stress induced
- idiopathic pulmonary fibrosis
- virtual reality