Advanced glycation end products regulate anabolic and catabolic activities <i>via</i> NLRP3‐inflammasome activation in human nucleus pulposus cells
-
- Yu Song
- Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
-
- Yan Wang
- Department of Physical Education China University of Geosciences Wuhan China
-
- Yukun Zhang
- Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
-
- Wen Geng
- China Medical University Shenyang China
-
- Wei Liu
- Department of Orthopedics First Hospital of Wuhan Wuhan China
-
- Yong Gao
- Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
-
- Shuai Li
- Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
-
- Kun Wang
- Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
-
- Xinghuo Wu
- Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
-
- Liang Kang
- Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
-
- Cao Yang
- Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
説明
<jats:title>Abstract</jats:title><jats:p>Intervertebral disc degeneration is widely recognized as a cause of lower back pain, neurological dysfunction and other musculoskeletal disorders. The major inflammatory cytokine IL‐1β is associated with intervertebral disc degeneration; however, the molecular mechanisms that drive IL‐1β production in the intervertebral disc, especially in nucleus pulposus (NP) cells, are unknown. In some tissues, advanced glycation end products (AGEs), which accumulate in NP tissues and promote its degeneration, increase oxidative stress and IL‐1β secretion, resulting in disorders, such as obesity, diabetes mellitus and ageing. It remains unclear whether AGEs exhibit similar effects in NP cells. In this study, we observed significant activation of the NLRP3 inflammasome in NP tissues obtained from patients with degenerative disc disease compared to that with idiopathic scoliosis according to results detected by Western blot and immunofluorescence. Using NP cells established from healthy tissues, our <jats:italic>in vitro</jats:italic> study revealed that AGEs induced an inflammatory response in NP cells and a degenerative phenotype in a NLRP3‐inflammasome‐dependent manner related to the receptor for AGEs (RAGE)/NF‐κB pathway and mitochondrial damage induced by mitochondrial reactive oxygen species (mtROS) generation, mitochondrial permeability transition pore (mPTP) activation and calcium mobilization. Among these signals, both RAGE and mitochondrial damage primed NLRP3 and pro‐IL‐1β activation as upstream signals of NF‐κB activity, whereas mitochondrial damage was critical for the assembly of inflammasome components. These results revealed that accumulation of AGEs in NP tissue may initiate inflammation‐related degeneration of the intervertebral disc <jats:italic>via</jats:italic> activation of the NLRP3 inflammasome.</jats:p>
収録刊行物
-
- Journal of Cellular and Molecular Medicine
-
Journal of Cellular and Molecular Medicine 21 (7), 1373-1387, 2017-02-22
Wiley