Department of Trauma, Yantaishan Hospital, Yantai, People's Republic of China.
Department of Spinal Surgery, Laiyang Central Hospital of Yantai City, Yantai, People's Republic of China.
Immunopharmacol Immunotoxicol. 2022 Oct;44(5):732-745. doi: 10.1080/08923973.2022.2078728. Epub 2022 Jul 11.
This study aimed to explore the underlying role and mechanism of LINC00313 in osteoarthritis (OA) progression.
CHON-001 chondrocytes were treated with interleukin (IL)-1β to induce OA , and then transfected with LINC00313 overexpression plasmids (pcDNA-LINC00313) or small interfering RNA against tumor necrosis factor (TNF) receptor-associated factor 1 (si-TRAF1). Cell viability, apoptosis, levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-6 and IL-8, and expression of extracellular matrix (ECM) degradation related proteins in CHON-001 cells were determined. TRAF1 promoter methylation were was detected with methylation-specific polymerase chain reaction (MSP) assay. Furthermore, a c-Jun N-terminal kinase (JNK) signaling activator was used to confirm whether the apoptosis signal-regulating kinase 1 (ASK1)/JNK signaling pathway was involved in the function of LINC00313/TRAF1 axis in chondrocytes. In addition, an OA mouse model was established and lentivirus LINC00313 overexpression vector (Lv-LINC00313) was injected, and then inflammatory cytokine levels, ECM protein expression, and pathological changes in cartilage tissues were detected.
LINC00313 was downregulated and TRAF1 was upregulated in OA cartilage tissues. LINC00313 overexpression or TRAF1 silencing attenuated IL-1β-induced viability inhibition, apoptosis, inflammation and ECM degradation in CHON-001 cells. Moreover, LINC00313 inhibited TRAF1 expression through promoting DNA methyltransferase 1 (DNMT1) mediated promoter methylation. TRAF1 overexpression reversed the effects of LINC00313 on IL-1β-induced chondrocyte injury. LINC00313 overexpression inhibited the ASK1/JNK signaling pathway, and JNK activator reversed the effect. In addition, Lv-LINC00313 treatment alleviated cartilage tissue damage and cartilage matrix degradation in OA mice.
LINC00313 alleviated OA progression through inhibiting TRAF1 expression and the ASK1/JNK signaling pathway.
本研究旨在探讨 LINC00313 在骨关节炎（OA）进展中的潜在作用和机制。
用白细胞介素（IL）-1β处理 CHON-001 软骨细胞诱导 OA，然后转染 LINC00313 过表达质粒（pcDNA-LINC00313）或肿瘤坏死因子（TNF）受体相关因子 1（si-TRAF1）的小干扰 RNA。测定 CHON-001 细胞的细胞活力、凋亡、炎症细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）水平以及细胞外基质（ECM）降解相关蛋白的表达。采用甲基化特异性聚合酶链反应（MSP）检测 TRAF1 启动子甲基化。此外，使用 c-Jun N 端激酶（JNK）信号激活剂来确认ASK1/JNK 信号通路是否参与 LINC00313/TRAF1 轴在软骨细胞中的功能。此外，建立 OA 小鼠模型并注射慢病毒 LINC00313 过表达载体（Lv-LINC00313），然后检测炎症细胞因子水平、ECM 蛋白表达和软骨组织的病理变化。
OA 软骨组织中 LINC00313 下调，TRAF1 上调。LINC00313 过表达或 TRAF1 沉默可减轻 IL-1β诱导的 CHON-001 细胞活力抑制、凋亡、炎症和 ECM 降解。此外，LINC00313 通过促进 DNA 甲基转移酶 1（DNMT1）介导的启动子甲基化抑制 TRAF1 表达。TRAF1 过表达逆转了 LINC00313 对 IL-1β诱导的软骨细胞损伤的影响。LINC00313 过表达抑制 ASK1/JNK 信号通路，JNK 激活剂逆转该作用。此外，Lv-LINC00313 治疗减轻了 OA 小鼠的软骨组织损伤和软骨基质降解。
LINC00313 通过抑制 TRAF1 表达和 ASK1/JNK 信号通路缓解 OA 进展。
