Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China; The First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China; Department of Orthopaedic Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.
Life Sci. 2021 Jun 1;274:119324. doi: 10.1016/j.lfs.2021.119324. Epub 2021 Mar 9.
Intervertebral Disc Degeneration (IDD) is a key factor involved in low back pain (LBP) which affects approximately 540 million individuals worldwide. Chlorogenic Acid (CGA), a natural compound, exerts anti-inflammatory property in several diseases. Here, we aim to investigate the biological effect of CGA on IDD and explore the underlying mechanism.
Lumbar spine instability (LSI) model in mice was utilized to mimic process of IDD. The effects of CGA in response to LSI were evaluated by luminescent imaging, micro-CT, histomorphology, and immunohistochemistry in vivo. Besides, the cytotoxicity of CGA on chondrocytes was detected by cell counting kit-8 (CCK-8) and the biological effects were assessed by polymerase chain reaction (PCR) in vitro.
We found that CGA treatment dramatically suppressed the NF-κB activity in LSI mice. Moreover, administration of CGA mitigated cartilaginous endplate degeneration and postponed IDD development accompanying a decrease of inflammatory and catabolic mediators. Specifically, CGA ameliorated endplate degeneration might be related to its protective effects against endplate chondrocytes apoptosis and trans-differentiation. We further elucidated that CGA exerted these biological effects mainly by repressing NF-κB signaling in cartilage endplate.
Our study has illustrated, for the first time, the curative effects as well as the latent mechanism of CGA in IDD and our results suggested that CGA administration might be used as an alternative therapy for IDD.
椎间盘退变（IDD）是导致全世界约 5.4 亿人出现下腰痛（LBP）的关键因素。绿原酸（CGA）是一种天然化合物，在多种疾病中具有抗炎作用。本研究旨在探讨 CGA 对 IDD 的生物学作用，并探讨其潜在机制。
采用小鼠腰椎失稳（LSI）模型模拟 IDD 过程。通过体内发光成像、微 CT、组织形态学和免疫组织化学评估 CGA 对 LSI 的作用。此外，通过细胞计数试剂盒-8（CCK-8）检测 CGA 对软骨细胞的细胞毒性，并通过聚合酶链反应（PCR）体外评估其生物学效应。
我们发现 CGA 治疗可显著抑制 LSI 小鼠的 NF-κB 活性。此外，CGA 给药可减轻软骨终板退变，延缓 IDD 发展，同时降低炎症和分解代谢介质。具体而言，CGA 改善终板退变可能与其对终板软骨细胞凋亡和转分化的保护作用有关。我们进一步阐明，CGA 主要通过抑制软骨终板中的 NF-κB 信号通路发挥这些生物学作用。
本研究首次阐明了 CGA 在 IDD 中的治疗效果及其潜在机制，研究结果表明，CGA 给药可能可作为 IDD 的一种替代治疗方法。
