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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

Experimental & Molecular Medicine 2019년 51권 9호 p.110 ~ 110
 ( Wu Xinghuo ) - Huazhong University of Science and Technology Tongji Medical College Union Hospital Department of Orthopedics

 ( Liao Zhiwei ) - Huazhong University of Science and Technology Tongji Medical College Union Hospital Department of Orthopedics
 ( Wang Kun ) - Huazhong University of Science and Technology Tongji Medical College Union Hospital Department of Orthopedics
 ( Hua Wenbin ) - Huazhong University of Science and Technology Tongji Medical College Union Hospital Department of Orthopedics
 ( Liu Xianzhe ) - Huazhong University of Science and Technology Tongji Medical College Union Hospital Department of Orthopedics
 ( Song Yu ) - Huazhong University of Science and Technology Tongji Medical College Union Hospital Department of Orthopedics
 ( Zhang Yukun ) - Huazhong University of Science and Technology Tongji Medical College Union Hospital Department of Orthopedics
 ( Yang Shuhua ) - Huazhong University of Science and Technology Tongji Medical College Union Hospital Department of Orthopedics

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.

키워드

Molecular biology; Pathogenesis
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