Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging
Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging
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DOI：
10.1038/s41598-019-55709-3
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发表时间：
2019-12-18
影响因子：
4.6
通讯作者：
Sudo, Hideki
中科院分区：
文献类型：
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作者：
Ohnishi, Takashi;Yamada, Katsuhisa;Sudo, Hideki
大约 40% 的 30 岁以下人群和超过 90% 的 55 岁以上人群患有中度至重度腰椎退行性椎间盘 (IVD) 疾病。手术治疗有时有效；然而，与IVD退化相关的背痛的治疗仍然是一个挑战；因此，需要新的治疗方法。细胞凋亡在 IVD 变性中可能很重要，因为抑制 IVD 内的细胞凋亡可以抑制变性。 Caspase-3 是细胞凋亡的主要效应因子，可能是一个关键的治疗靶点。我们使用 caspase-3 敲除 (Casp-3 KO) 小鼠分析了 caspase-3 在两种不同类型的 IVD 变性中的作用。 Casp-3 KO 在损伤诱导的模型中延迟了 IVD 变性，但在年龄诱导的模型中加速了 IVD 变性。我们的结果表明，这是由于这两类 IVD 变性的不同病理机制所致。 Casp-3 KO 小鼠的 IVD 细胞凋亡受到抑制，但细胞衰老增强。这可以解释为什么 Casp-3 KO 对损伤引起的 IVD 变性有效，但对年龄相关的 IVD 变性无效。我们的结果表明短期 caspase-3 抑制可用于治疗损伤引起的 IVD 变性。
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.