Department of Joint Surgery, Linyi People's Hospital, Linyi, Shandong, China.
Department of Hematology, Qingdao Central Hospital, Qingdao, Shandong, China.
Cell Cycle. 2022 Oct;21(19):2038-2050. doi: 10.1080/15384101.2022.2084294. Epub 2022 Jun 10.
Osteoarthritis (OA) is a common degenerative disease characterized by reducing articular chondrocytes and destruction of joint matrix, it's detailed pathogenesis remains unclear. Emerging evidences have demonstrated that long non-coding RNAs (lncRNAs) are closely related to the progression of OA. This study aims to explore the expression of long non-coding RNA LEMD1 antisense RNA 1 (LEMD1-AS1) in OA tissues and chondrocytes and investigate the possible mechanisms of LEMD1-AS1 in OA, which will provide a new target for the treatment of OA. In our study, LEMD1-AS1 and post-GPI attachment to protein (PGAP1) were lowly expressed, but miR-944 was highly expressed both in OA tissues and in Lipopolysaccharide (LPS) -treated chondrocytes detected by qRT-PCR. Over-expression of LEMD1-AS1 or down-regulation of miR-944 significantly promoted viability, proliferation and inhibited cell apoptosis, cell cycle arrest and inflammatory responses of chondrocytes treated with LPS by CCK-8, EdU, flow cytometry and an ELISA assay. Over-expression of LEMD1-AS1 or down-regulation of miR-944 remarkably increased the protein levels of PCNA, Ki-67, Cyclin A1, Cyclin B1, Cyclin D2 and Bcl-2, while decreasing the protein levels of p27, Bax, Cleaved-caspase-3 and Cleaved-caspase-9 in chondrocytes treated with LPS. LEMD1-AS1 bound to miR-944 and regulated its expression, and PGAP1 presented as a direct target gene of miR-944, which was confirmed by a dual-luciferase reporter assay. Inhibition of PGAP1 partially restored the effects of LEMD1-AS1/miR-944 on the proliferation, cell apoptosis, cell cycle distribution and inflammatory responses of LPS-treated chondrocytes. To conclude, the LEMD1-AS1/miR-944/PGAP1 axis may be a novel therapeutic candidate to target in OA treatment.
骨关节炎(OA)是一种常见的退行性疾病,其特征为关节软骨细胞减少和关节基质破坏,其详细发病机制尚不清楚。新出现的证据表明,长非编码 RNA(lncRNA)与 OA 的进展密切相关。本研究旨在探讨长非编码 RNA LEMD1 反义 RNA 1(LEMD1-AS1)在 OA 组织和软骨细胞中的表达,并探讨 LEMD1-AS1 在 OA 中的可能机制,这将为 OA 的治疗提供新的靶点。在我们的研究中,通过 qRT-PCR 检测到 OA 组织和脂多糖(LPS)处理的软骨细胞中 LEMD1-AS1 和 post-GPI 附着蛋白(PGAP1)表达降低,而 miR-944 表达升高。CCK-8、EdU、流式细胞术和 ELISA 检测结果表明,过表达 LEMD1-AS1 或下调 miR-944 可显著促进 LPS 处理的软骨细胞的活力、增殖,并抑制细胞凋亡、细胞周期阻滞和炎症反应。过表达 LEMD1-AS1 或下调 miR-944 可显著增加 LPS 处理的软骨细胞中 PCNA、Ki-67、Cyclin A1、Cyclin B1、Cyclin D2 和 Bcl-2 的蛋白水平,同时降低 p27、Bax、Cleaved-caspase-3 和 Cleaved-caspase-9 的蛋白水平。LEMD1-AS1 与 miR-944 结合并调节其表达,PGAP1 是 miR-944 的直接靶基因,这通过双荧光素酶报告基因实验得到证实。抑制 PGAP1 部分恢复了 LEMD1-AS1/miR-944 对 LPS 处理的软骨细胞增殖、细胞凋亡、细胞周期分布和炎症反应的影响。总之,LEMD1-AS1/miR-944/PGAP1 轴可能是 OA 治疗的一个新的治疗靶点。