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Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging

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Title: Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging
Authors: Ohnishi, Takashi Browse this author
Yamada, Katsuhisa Browse this author
Iwasaki, Koji Browse this author →KAKEN DB
Tsujimoto, Takeru Browse this author
Higashi, Hideaki Browse this author →KAKEN DB
Kimura, Taichi Browse this author →KAKEN DB
Iwasaki, Norimasa Browse this author →KAKEN DB
Sudo, Hideki Browse this author →KAKEN DB
Issue Date: 18-Dec-2019
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 9
Start Page: 19324
Publisher DOI: 10.1038/s41598-019-55709-3
Abstract: Approximately 40% of people under 30 and over 90% of people 55 or older suffer from moderate-to-severe levels of degenerative intervertebral disc (IVD) disease in their lumbar spines. Surgical treatments are sometimes effective; however, the treatment of back pain related to IVD degeneration is still a challenge; therefore, new treatments are necessary. Apoptosis may be important in IVD degeneration because suppressing cell apoptosis inside the IVD inhibits degeneration. Caspase-3, the primary effector of apoptosis, may be a key treatment target. We analyzed caspase-3's role in two different types of IVD degeneration using caspase-3 knockout (Casp-3 KO) mice. Casp-3 KO delayed IVD degeneration in the injury-induced model but accelerated it in the age-induced model. Our results suggest that this is due to different pathological mechanisms of these two types of IVD degeneration. Apoptosis was suppressed in the IVD cells of Casp-3 KO mice, but cellular senescence was enhanced. This would explain why the Casp-3 KO was effective against injury-induced, but not age-related, IVD degeneration. Our results suggest that short-term caspase-3 inhibition could be used to treat injury-induced IVD degeneration.
Rights: https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/76809
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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