Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, PR China; Department of Orthopaedics, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng 224005, PR China.
Department of Orthopaedics, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng 224005, PR China.
Cytokine. 2021 Dec;148:155686. doi: 10.1016/j.cyto.2021.155686. Epub 2021 Sep 11.
Osteoarthritis (OA) is the most common joint disease in the elderly and is characterized by the progressive degeneration of articular cartilage. It is necessary to study the molecular pathology of OA. This study aimed to explore the role and mechanism of BLNK in regulating interleukin-1β (IL-1β)-induced chondrocyte injury and OA progression.
GSE1919 (5 normal samples and 5 OA samples) was downloaded from the Gene Expression Omnibus (GEO) database. The limma package in R software was used to identify differentially expressed genes (DEGs) between control and OA-affected cartilage. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the differentially expressed genes were also performed. Apoptosis was assessed by flow cytometry. An OA rat model was established, and the relative expression of BLNK was assessed by real time quantitative PCR (qRT-PCR) and immunohistochemical staining. The expression of collagen II, MMP9, p65 and p-p65 was measured by Western blot analysis. Moreover, inflammatory factors (TNF-α and IL-18) were assessed by ELISA. The NF-κB inhibitor JSH-23 was used to assess the impact of BLNK on the NF-κB signaling pathway.
In total, 1318 DEGs were identified between normal and OA-affected cartilage according to the criteria (P-value <0.05 and |logFC > 1|). These DEGs were mainly enriched in the NF-κB pathway. BLNK was highly expressed in OA cartilage tissue and injured chondrocytes. Silencing BLNK significantly downregulated the IL-1β-induced apoptosis of chondrocytes. Silencing BLNK partially increased collagen II expression and downregulated MMP13 expression. Moreover, silencing BLNK partially decreased TNF-α and IL-18 expression. BLNK silencing inhibited the activation of NF-κB in OA. Silencing BLNK delayed OA progression through the NF-κB signaling pathway.
Silencing BLNK delayed OA progression and IL-1β-induced chondrocyte injury by regulating the NF-κB pathway.
骨关节炎（OA）是老年人最常见的关节疾病，其特征是关节软骨进行性退化。有必要研究 OA 的分子病理学。本研究旨在探讨 BLNK 在调节白细胞介素 1β（IL-1β）诱导的软骨细胞损伤和 OA 进展中的作用和机制。
从基因表达综合数据库（GEO）下载 GSE1919（5 个正常样本和 5 个 OA 样本）。使用 R 软件中的 limma 包鉴定对照和 OA 软骨之间差异表达基因（DEGs）。还进行了差异表达基因的基因本体论和京都基因与基因组百科全书（KEGG）通路分析。通过流式细胞术评估细胞凋亡。建立 OA 大鼠模型，通过实时定量 PCR（qRT-PCR）和免疫组织化学染色评估 BLNK 的相对表达。通过 Western blot 分析测量胶原 II、MMP9、p65 和 p-p65 的表达。此外，通过 ELISA 评估炎症因子（TNF-α 和 IL-18）。使用 NF-κB 抑制剂 JSH-23 评估 BLNK 对 NF-κB 信号通路的影响。
根据标准（P 值<0.05 和 |logFC>1|），在正常和 OA 软骨之间共鉴定出 1318 个 DEGs。这些 DEGs 主要富集在 NF-κB 通路中。BLNK 在 OA 软骨组织和损伤的软骨细胞中高表达。沉默 BLNK 可显著下调 IL-1β 诱导的软骨细胞凋亡。沉默 BLNK 部分增加胶原 II 的表达，下调 MMP13 的表达。此外，沉默 BLNK 部分降低 TNF-α 和 IL-18 的表达。BLNK 沉默抑制 OA 中的 NF-κB 激活。通过 NF-κB 信号通路，沉默 BLNK 可延缓 OA 进展。
沉默 BLNK 通过调节 NF-κB 通路延缓 OA 进展和 IL-1β 诱导的软骨细胞损伤。
