Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.
Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan.
Aging (Albany NY). 2021 Sep 24;13(18):22490-22501. doi: 10.18632/aging.203559.
The progression of osteoarthritis (OA) is mediated by adipokines, one of which is nesfatin-1, which is responsible for the production of inflammatory cytokines. However, how this molecule may affect the synthesis of the proinflammatory cytokine interleukin 1 beta (IL-1β) in OA is unclear. Our analyses of records from the Gene Expression Omnibus (GEO) dataset and clinical specimens of synovial tissue revealed higher levels of nesfatin-1 and IL-1β in OA samples compared with normal healthy tissue. We found that nesfatin-1 facilitates IL-1β synthesis in human OA synovial fibroblasts (OASFs) and suppresses the generation of micro-RNA (miR)-204-5p, as the miR-204-5p levels in OA patients were lower than those in healthy controls. Nesfatin-1-induced stimulation of IL-1β in human OASFs occurred via the suppression of miR-204-5p synthesis by the PI3K, Akt, AP-1 and NF-κB pathways. We suggest that nesfatin-1 is worth targeting in OA treatment.
骨关节炎（OA）的进展是由脂肪因子介导的，其中一种是 nesfatin-1，它负责产生炎症细胞因子。然而，这种分子如何影响 OA 中促炎细胞因子白细胞介素 1β（IL-1β）的合成尚不清楚。我们对基因表达综合数据库（GEO）数据集和滑膜组织临床标本的分析显示，OA 样本中 nesfatin-1 和 IL-1β 的水平高于正常健康组织。我们发现 nesfatin-1 促进人 OA 滑膜成纤维细胞（OASFs）中 IL-1β 的合成，并抑制 micro-RNA（miR）-204-5p 的产生，因为 OA 患者的 miR-204-5p 水平低于健康对照组。nesfatin-1 通过 PI3K、Akt、AP-1 和 NF-κB 途径抑制 miR-204-5p 的合成，从而诱导人 OASFs 中 IL-1β 的刺激。我们认为 nesfatin-1 值得作为 OA 治疗的靶点。
