Ionizing Radiation Induces Disc Annulus Fibrosus Senescence and Matrix Catabolism via MMP-Mediated Pathways.

Ionizing Radiation Induces Disc Annulus Fibrosus Senescence and Matrix Catabolism via MMP-Mediated Pathways.
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电离辐射可通过MMP介导的途径诱导椎间盘环纤维衰老和基质分解代谢。

DOI:
10.3390/ijms23074014
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发表时间:
2022-04-05
影响因子:
5.6
通讯作者:
Vo NV
Vo NV
中科院分区:
生物学2区
文献类型:
--
作者:
Zhong J;Chen J;Oyekan AA;Epperly MW;Greenberger JS;Lee JY;Sowa GA;Vo NV

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以前的研究已经确定了外部辐射和椎间盘退变之间的联系,但其机制知之甚少。本研究探讨了电离辐射(IR)诱导细胞衰老的纤维环(AF)在细胞培养和在体小鼠模型。AF细胞培养物暴露于10-15戈伊IR 5 min,随后培养物孵育5天,导致几乎完全的衰老诱导,如细胞的SA-βgal阳性染色和p16和p21衰老标记物的mRNA表达升高所证明的。IR诱导的衰老AF细胞表现出增加的基质分解,包括基质金属蛋白酶(MMP)-1和3蛋白表达升高和聚集蛋白溶解。在全身IR暴露的小鼠中观察到类似的结果,表明遗传毒性应激也驱动体内椎间盘细胞衰老和基质降解。这些结果在电离辐射对脊柱健康的潜在不良影响方面具有重要的临床意义。
Previous research has identified an association between external radiation and disc degeneration, but the mechanism was poorly understood. This study explores the effects of ionizing radiation (IR) on inducing cellular senescence of annulus fibrosus (AF) in cell culture and in an in vivo mouse model. Exposure of AF cell culture to 10–15 Gy IR for 5 min followed by 5 days of culture incubation resulted in almost complete senescence induction as evidenced by SA-βgal positive staining of cells and elevated mRNA expression of the p16 and p21 senescent markers. IR-induced senescent AF cells exhibited increased matrix catabolism, including elevated matrix metalloproteinase (MMP)-1 and -3 protein expression and aggrecanolysis. Analogous results were seen with whole body IR-exposed mice, demonstrating that genotoxic stress also drives disc cellular senescence and matrix catabolism in vivo. These results have important clinical implications in the potential adverse effects of ionizing radiation on spinal health.
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