a Department of Orthopaedics, The Affiliated Shanghai General Hospital of Nanjing Medical University , Shanghai , China.
b Department of Orthopaedics, The Fourth Affiliated Hospital of Nantong University , Yancheng , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3004-3012. doi: 10.1080/21691401.2019.1643733.
Cervical spondylosis is a degenerative disease commonly found in older adults and characterized by progressive osteophyte formation and disc collapse. Apoptosis in nucleus pulposus (NP) cells which induced by TNF-α has been widely known to associate with the disc degeneration. However, the exactly underlying molecular mechanism was still unclear. The aim of our study was to investigate whether TRIM14/NF-κB signalling pathway is associated with the apoptosis of human NP cells (HNPC) induced by TNF-α. Our data demonstrated that TNF-α treatment obviously decreased the cell viability, induced apoptosis and increased TRIM14 expression and NF-κBp65 activity in HNPC in a dose-dependent manner. Down-regulation of TRIM14 or NF-κB inhibitor PDTC treatment significantly inhibited cell apoptosis, Bax/Bcl-2 ratio and NF-κBp65 activation induced by TNF-α in HNPC. Meanwhile, up-regulation of TRIM14 obviously increased cell apoptosis, Bax/Bcl-2 ratio and NF-κBp65 activation in HNPC. Then, we found that the protein PPM1A was identified as a binding partner of TRIM14 and ubiquitinated by TRIM14. These findings provide insights into the function of TRIM14 and NF-κB signalling and might, therefore, represent a novel therapeutic target for treatment of cervical spondylosis.
颈椎病是一种常见于老年人的退行性疾病，其特征为进行性骨赘形成和椎间盘塌陷。TNF-α诱导的髓核细胞（NP）细胞凋亡与椎间盘退变广泛相关。然而，确切的潜在分子机制尚不清楚。本研究旨在探讨 TRIM14/NF-κB 信号通路是否与 TNF-α诱导的人 NP 细胞（HNPC）凋亡有关。我们的数据表明，TNF-α 处理明显以剂量依赖性方式降低 HNPC 的细胞活力，诱导细胞凋亡，并增加 TRIM14 表达和 NF-κBp65 活性。下调 TRIM14 或 NF-κB 抑制剂 PDTC 处理可显著抑制 TNF-α诱导的 HNPC 细胞凋亡、Bax/Bcl-2 比值和 NF-κBp65 激活。同时，TRIM14 的上调明显增加了 HNPC 中的细胞凋亡、Bax/Bcl-2 比值和 NF-κBp65 激活。然后，我们发现蛋白 PPM1A 被鉴定为 TRIM14 的结合伴侣，并被 TRIM14 泛素化。这些发现为 TRIM14 和 NF-κB 信号通路的功能提供了深入了解，因此可能成为治疗颈椎病的新治疗靶点。
