Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
J Cell Physiol. 2020 Nov;235(11):8402-8415. doi: 10.1002/jcp.29684. Epub 2020 Apr 2.
Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase-1 (HO-1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO-1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO-1 expression was reduced in IDD tissues and replicative senescent NP cells. HO-1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3-MA pretreatment reversed the anti-senescent and protective effects on the mitochondrial function of HO-1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO-1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO-1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.
椎间盘退变（IDD）与衰老密切相关。我们之前的研究已经证实血红素加氧酶-1（HO-1）可以抑制髓核（NP）细胞凋亡。然而，HO-1 是否参与 NP 细胞衰老和自噬尚不清楚。我们的结果表明，HO-1 的表达在 IDD 组织和复制性衰老的 NP 细胞中降低。使用慢病毒载体过表达 HO-1 可以降低 NP 细胞衰老水平，保护线粒体功能，并通过线粒体途径促进 NP 细胞自噬。自噬抑制剂 3-MA 预处理逆转了 HO-1 对线粒体功能的抗衰老和保护作用，促进了椎间盘细胞外基质（ECM）的降解。在体内，HO-1 的过表达抑制了 IDD 并增强了自噬。综上所述，这些结果表明，HO-1 的过表达通过诱导线粒体途径的自噬来减轻 NP 细胞衰老。
