Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital.
Biol Pharm Bull. 2021 Feb 1;44(2):232-237. doi: 10.1248/bpb.b20-00688. Epub 2020 Dec 2.
Osteoarthritis (OA) is a chronic joint disease with high prevalence. However, effective treatment options for OA are still lacking. It was previously reported that LINC00473 was upregulated in patients with OA and upregulated LINC00473 might be associated with the progression of OA; however, the role of LINC00473 in OA remains to be investigated. CHON-001 human chondrocyte cells stimulated with 10 ng/mL interleukin (IL)-1β were utilized to mimic OA in vitro. Protein expression, cell apoptosis and cell proliferation of CHON-001 cells were investigated by Western blot, Annexin V and propidium iodide (PI) double staining, cell counting-8 kit assay and immunofluorescence staining respectively. The result indicated IL-1β triggered viability decrease and apoptosis in CHON-001 cells, which was alleviated by LINC00473 knockdown. Meanwhile, IL-1β-induced upregulation of cleaved caspase 3 and Bax were ameliorated by LINC00473 knockdown. Likewise, IL-1β-induced downregulation of X-linked inhibitor of apoptosis protein was alleviated by LINC00473 knockdown. In addition, LINC00473 knockdown protected CHON-001 cells against IL-1β by inhibiting the methylation of LIM mineralization protein (LMP)-1 gene. Moreover, c-Jun N-terminal kinase (JNK)/nuclear factor-kappaB (NF-κB) signaling pathway was proved to be involved in the cell protective effect of LINC00473 knockdown in IL-1β treated CHON-001 cells. Taken together, LINC00473 knockdown defended CHON-001 cells from IL-1β induced cell injury via inhibition of the methylation of LMP-1. Thus, LINC00473 might possibly act as a novel therapeutic target for OA.
骨关节炎（OA）是一种患病率较高的慢性关节疾病。然而，OA 的有效治疗选择仍然缺乏。此前有报道称，LINC00473 在 OA 患者中上调，上调的 LINC00473 可能与 OA 的进展有关；然而，LINC00473 在 OA 中的作用仍有待研究。本研究采用 10ng/ml 白细胞介素（IL）-1β刺激 CHON-001 人软骨细胞，在体外模拟 OA。通过 Western blot、Annexin V 和碘化丙啶（PI）双重染色、细胞计数-8 试剂盒检测和免疫荧光染色分别检测 CHON-001 细胞的蛋白表达、细胞凋亡和细胞增殖。结果表明，IL-1β 触发 CHON-001 细胞活力下降和凋亡，LINC00473 敲低可减轻这种作用。同时，LINC00473 敲低减轻了 IL-1β 诱导的 cleaved caspase 3 和 Bax 的上调。同样，LINC00473 敲低减轻了 IL-1β 诱导的 X 连锁凋亡抑制蛋白下调。此外，LINC00473 敲低通过抑制 LIM 矿化蛋白（LMP）-1 基因的甲基化来保护 CHON-001 细胞免受 IL-1β 的侵害。此外，研究证实 c-Jun N-末端激酶（JNK）/核因子-κB（NF-κB）信号通路参与了 LINC00473 敲低在 IL-1β 处理的 CHON-001 细胞中对细胞的保护作用。综上所述，LINC00473 敲低通过抑制 LMP-1 的甲基化来保护 CHON-001 细胞免受 IL-1β 诱导的细胞损伤。因此，LINC00473 可能成为 OA 的一个新的治疗靶点。
