Zhang Baining, He Zhiwei, Guo Jialin, Li Feng, Huang Zhi, Zheng Wenkai, Xing Wenhua, Li Manglai, Zhu Yong, Yang Xuejun
Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
Department of Spine Surgery, Area A, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
Aging (Albany NY). 2024 Jan 26;16(2):1145-1160. doi: 10.18632/aging.205386.
Lumbar disc degeneration (LDD) is a prevalent clinical spinal disease characterized by the calcification and degeneration of the cartilage endplate (CEP), which significantly reduces nutrient supply to the intervertebral disc. Traditional Chinese medicine offers a conservative and effective approach for treating LDD. We aimed to investigate the molecular mechanisms underlying the therapeutic effects of Sesamin in LDD treatment. Transcriptome sequencing was used to analyze the effect of Sesamin on LPS-induced ATDC5. We explored the role of BECN2, a target gene of Sesamin, in attenuating LPS-induced degeneration of ATDC5 cells. Our results revealed the identification of 117 differentially expressed genes (DEGs), with 54 up-regulated and 63 down-regulated genes. Notably, Sesamin significantly increased the expression of BECN2 in LPS-induced ATDC5 cell degeneration. Overexpressed BECN2 enhanced cell viability and inhibited cell apoptosis in LPS-induced ATDC5 cells, while BECN2 knockdown reduced cell viability and increased apoptosis. Furthermore, BECN2 played a crucial role in attenuating chondrocyte degeneration by modulating autophagy and inflammation. Specifically, BECN2 suppressed autophagy by reducing the expression of ATG14, VPS34, and GASP1, and alleviated the inflammatory response by decreasing the expression of inflammasome proteins NLRP3, NLRC4, NLRP1, and AIM2. experiments further supported the beneficial effects of Sesamin in mitigating LDD. This study provides novel insights into the potential molecular mechanism of Sesamin in treating LDD, highlighting its ability to mediate autophagy and inflammation inhibition via targeting the BECN2. This study provides a new therapeutic strategy for the treatment of LDD, as well as a potential molecular target for LDD.
腰椎间盘退变（LDD）是一种常见的临床脊柱疾病，其特征为软骨终板（CEP）钙化和退变，这会显著减少椎间盘的营养供应。中医为LDD的治疗提供了一种保守且有效的方法。我们旨在研究芝麻素治疗LDD的分子机制。采用转录组测序分析芝麻素对脂多糖（LPS）诱导的ATDC5细胞的影响。我们探讨了芝麻素的靶基因BECN2在减轻LPS诱导的ATDC5细胞退变中的作用。我们的结果显示共鉴定出117个差异表达基因（DEG），其中54个基因上调，63个基因下调。值得注意的是，芝麻素显著增加了LPS诱导的ATDC5细胞退变中BECN2的表达。过表达BECN2可增强LPS诱导的ATDC5细胞的活力并抑制细胞凋亡，而敲低BECN2则降低细胞活力并增加细胞凋亡。此外，BECN2通过调节自噬和炎症在减轻软骨细胞退变中起关键作用。具体而言，BECN2通过降低ATG14、VPS34和GASP1的表达来抑制自噬，并通过降低炎性小体蛋白NLRP3、NLRC4、NLRP1和AIM2的表达来减轻炎症反应。实验进一步支持了芝麻素在减轻LDD方面的有益作用。本研究为芝麻素治疗LDD的潜在分子机制提供了新的见解，突出了其通过靶向BECN2介导自噬和炎症抑制的能力。本研究为LDD的治疗提供了一种新的治疗策略，以及LDD的一个潜在分子靶点。
