Department of Orthopedic Surgery, Xuzhou Third People's Hospital, Affiliated Xuzhou Hospital of Jiangsu University, Affiliated Xuzhou Third People's Hospital of Xuzhou Medical University, Xuzhou City 221005, Jiangsu, China.
Department of Orthopedic Surgery, Xuzhou Third People's Hospital, Affiliated Xuzhou Hospital of Jiangsu University, Affiliated Xuzhou Third People's Hospital of Xuzhou Medical University, Xuzhou City 221005, Jiangsu, China.
Clin Immunol. 2021 Dec;233:108889. doi: 10.1016/j.clim.2021.108889. Epub 2021 Nov 17.
The dysregulation of circular RNA (circRNA) has been monitored in osteoarthritis (OA) cartilage, hinting that circRNA deregulation modulates OA progression. We thus aimed to unveil the role of circRNA spastic paraplegia 11 (circ_SPG11) in OA conditions. The upregulation of circ_SPG11 was observed in OA cartilage and IL-1β-treated chondrocytes. Knockdown of circ_SPG11 restored IL-1β-depleted cell proliferation and alleviated IL-1β-induced cell apoptosis and ECM degradation. Circ_SPG11 bound to miR-665 and negatively regulated miR-665 expression. Inhibition of miR-665 reversed the inhibitory effect on IL-1β-induced chondrocyte injury caused by circ_SPG11 knockdown. GREM1 was a target of miR-665, and circ_SPG11 knockdown depleted GREM1 expression by enriching miR-665. Overexpression of GREM1 also reversed the inhibitory effect on IL-1β-induced chondrocyte injury caused by miR-665 enrichment. Circ_SPG11 might promote IL-1β-induced chondrocyte apoptosis and ECM degradation via increasing GREM1 expression by decoying miR-665.
环状 RNA (circRNA) 的失调已在骨关节炎 (OA) 软骨中得到监测，提示 circRNA 失调调节 OA 的进展。因此，我们旨在揭示环状 RNA 痉挛性截瘫 11 (circ_SPG11) 在 OA 条件下的作用。在 OA 软骨和 IL-1β 处理的软骨细胞中观察到 circ_SPG11 的上调。circ_SPG11 的敲低恢复了 IL-1β 耗竭的细胞增殖，并减轻了 IL-1β 诱导的细胞凋亡和 ECM 降解。circ_SPG11 与 miR-665 结合并负调控 miR-665 的表达。抑制 miR-665 逆转了 circ_SPG11 敲低对 IL-1β 诱导的软骨细胞损伤的抑制作用。GREM1 是 miR-665 的靶标，circ_SPG11 敲低通过富集 miR-665 耗尽 GREM1 表达。GREM1 的过表达也逆转了 miR-665 富集对 IL-1β 诱导的软骨细胞损伤的抑制作用。circ_SPG11 可能通过诱饵 miR-665 增加 GREM1 表达来促进 IL-1β 诱导的软骨细胞凋亡和 ECM 降解。
