The unfolded protein response mediated by PERK is casually related to the pathogenesis of intervertebral disc degeneration
-
- Takeshi Fujii
- Department of Orthopaedic Surgery Keio University School of Medicine 35 Shinanomachi, Shinjyuku‐ku Tokyo 160‐8582 Japan
-
- Nobuyuki Fujita
- Department of Orthopaedic Surgery Keio University School of Medicine 35 Shinanomachi, Shinjyuku‐ku Tokyo 160‐8582 Japan
-
- Satoshi Suzuki
- Department of Orthopaedic Surgery Keio University School of Medicine 35 Shinanomachi, Shinjyuku‐ku Tokyo 160‐8582 Japan
-
- Takashi Tsuji
- Department of Orthopaedic Surgery Fujita Health University Aichi Japan
-
- Takashi Takaki
- Section of Electron Microscopy Showa University Tokyo Japan
-
- Kazuo Umezawa
- Department of Molecular Target Medicine Aichi Medical University School of Medicine Aichi Japan
-
- Kota Watanabe
- Department of Orthopaedic Surgery Keio University School of Medicine 35 Shinanomachi, Shinjyuku‐ku Tokyo 160‐8582 Japan
-
- Takeshi Miyamoto
- Department of Orthopaedic Surgery Keio University School of Medicine 35 Shinanomachi, Shinjyuku‐ku Tokyo 160‐8582 Japan
-
- Keisuke Horiuchi
- Department of Orthopaedic Surgery National Defence Medical College Saitama Japan
-
- Morio Matsumoto
- Department of Orthopaedic Surgery Keio University School of Medicine 35 Shinanomachi, Shinjyuku‐ku Tokyo 160‐8582 Japan
-
- Masaya Nakamura
- Department of Orthopaedic Surgery Keio University School of Medicine 35 Shinanomachi, Shinjyuku‐ku Tokyo 160‐8582 Japan
書誌事項
- 公開日
- 2017-11-28
- 資源種別
- journal article
- 権利情報
-
- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
-
- 10.1002/jor.23787
- 公開者
- Wiley
この論文をさがす
説明
<jats:title>ABSTRACT</jats:title><jats:sec><jats:label /><jats:p>Although the number of patients with intervertebral disc (IVD) degeneration is increasing in aging societies, its etiology and pathogenesis remain elusive and there is currently no effective treatment to prevent this undesirable condition. The unfolded protein response (UPR) is a cellular machinery that plays critical roles in handling endoplasmic reticulum (ER) stress, a condition caused by the accumulation of unfolded proteins in the ER lumen. This study aimed to elucidate the potential role of the UPR mediated by pancreatic endoplasmic reticulum kinase (PERK), one of the major ER stress sensors in mammalian cells, in the development of IVD degeneration. IVD degeneration was artificially induced in Wister rats by percutaneously puncturing the coccyx IVDs and human IVDs were collected from patients who underwent spinal surgery. Expression of the UPR target genes was elevated in degenerative IVDs in both humans and rats. The induction of ER stress in annulus fibrosus cells significantly increased the transcripts for tumor necrosis factor alpha (TNF‐α) and interleukin 6 (IL‐6) in a nuclear factor (NF)‐κB pathway‐dependent manner. The expression of TNF‐α and IL‐6 was significantly reduced by treatment with a selective PERK inhibitor, GSK2606414, and by gene silencing against PERK and activating transcription factor 4 (ATF4) transcripts. Our findings indicate that the UPR mediated by the PERK pathway is causally related to the development of IVD degeneration, suggesting that PERK may be a potential molecular target for suppressing the degenerative changes in IVDs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1334–1345, 2018.</jats:p></jats:sec>
収録刊行物
-
- Journal of Orthopaedic Research
-
Journal of Orthopaedic Research 36 (5), 1334-1345, 2017-11-28
Wiley
